Unlocking the potential of bispecific ADCs for targeted cancer therapy

Hongye Zeng, Wenjing Ning, Xue Liu, Wenxin Luo, Ningshao Xia

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Front. Med. ›› 2024, Vol. 18 ›› Issue (4) : 597-621. DOI: 10.1007/s11684-024-1072-8
REVIEW

Unlocking the potential of bispecific ADCs for targeted cancer therapy

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Abstract

Antibody–drug conjugates (ADCs) are biologically targeted drugs composed of antibodies and cytotoxic drugs connected by linkers. These innovative compounds enable precise drug delivery to tumor cells, minimizing harm to normal tissues and offering excellent prospects for cancer treatment. However, monoclonal antibody-based ADCs still present challenges, especially in terms of balancing efficacy and safety. Bispecific antibodies are alternatives to monoclonal antibodies and exhibit superior internalization and selectivity, producing ADCs with increased safety and therapeutic efficacy. In this review, we present available evidence and future prospects regarding the use of bispecific ADCs for cancer treatment, including a comprehensive overview of bispecific ADCs that are currently in clinical trials. We offer insights into the future development of bispecific ADCs to provide novel strategies for cancer treatment.

Keywords

antibody–drug conjugate / bispecific antibody / bispecific ADC / cancer

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Hongye Zeng, Wenjing Ning, Xue Liu, Wenxin Luo, Ningshao Xia. Unlocking the potential of bispecific ADCs for targeted cancer therapy. Front. Med., 2024, 18(4): 597‒621 https://doi.org/10.1007/s11684-024-1072-8

References

[1]
Strebhardt K, Ullrich A. Paul Ehrlich’s magic bullet concept: 100 years of progress. Nat Rev Cancer 2008; 8(6): 473–480
CrossRef Google scholar
[2]
Schwartz RS. Paul Ehrlich’s magic bullets. N Engl J Med 2004; 350(11): 1079–1080
CrossRef Google scholar
[3]
Chu Y, Zhou X, Wang X. Antibody-drug conjugates for the treatment of lymphoma: clinical advances and latest progress. J Hematol Oncol 2021; 14(1): 88
CrossRef Google scholar
[4]
Rosner S, Valdivia A, Hoe HJ, Murray JC, Levy B, Felip E, Solomon BJ. Antibody-drug conjugates for lung cancer: payloads and progress. Am Soc Clin Oncol Educ Book 2023; 43: e389968
CrossRef Google scholar
[5]
Liu H, Bolleddula J, Nichols A, Tang L, Zhao Z, Prakash C. Metabolism of bioconjugate therapeutics: why, when, and how?. Drug Metab Rev 2020; 52(1): 66–124
CrossRef Google scholar
[6]
Su Z, Xiao D, Xie F, Liu L, Wang Y, Fan S, Zhou X, Li S. Antibody-drug conjugates: recent advances in linker chemistry. Acta Pharm Sin B 2021; 11(12): 3889–3907
CrossRef Google scholar
[7]
Fu Z, Li S, Han S, Shi C, Zhang Y. Antibody drug conjugate: the “biological missile” for targeted cancer therapy. Signal Transduct Target Ther 2022; 7(1): 93
CrossRef Google scholar
[8]
Hurvitz SA. Recent progress in antibody-drug conjugate therapy for cancer. Nat Cancer 2022; 3(12): 1412–1413
CrossRef Google scholar
[9]
Ali S, Dunmore HM, Karres D, Hay JL, Salmonsson T, Gisselbrecht C, Sarac SB, Bjerrum OW, Hovgaard D, Barbachano Y, Nagercoil N, Pignatti F. The EMA review of Mylotarg (gemtuzumab ozogamicin) for the treatment of acute myeloid leukemia. Oncologist 2019; 24(5): e171–e179
CrossRef Google scholar
[10]
Godwin CD, Gale RP, Walter RB. Gemtuzumab ozogamicin in acute myeloid leukemia. Leukemia 2017; 31(9): 1855–1868
CrossRef Google scholar
[11]
Tsuchikama K, An Z. Antibody-drug conjugates: recent advances in conjugation and linker chemistries. Protein Cell 2018; 9(1): 33–46
CrossRef Google scholar
[12]
Beck A, Goetsch L, Dumontet C, Corvaïa N. Strategies and challenges for the next generation of antibody-drug conjugates. Nat Rev Drug Discov 2017; 16(5): 315–337
CrossRef Google scholar
[13]
Epaillard N, Bassil J, Pistilli B. Current indications and future perspectives for antibody-drug conjugates in brain metastases of breast cancer. Cancer Treat Rev 2023; 119: 102597
CrossRef Google scholar
[14]
Castaigne S, Pautas C, Terré C, Raffoux E, Bordessoule D, Bastie JN, Legrand O, Thomas X, Turlure P, Reman O, de Revel T, Gastaud L, de Gunzburg N, Contentin N, Henry E, Marolleau JP, Aljijakli A, Rousselot P, Fenaux P, Preudhomme C, Chevret S, Dombret H; Acute Leukemia French Association. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet 2012; 379(9825): 1508–1516
CrossRef Google scholar
[15]
Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, Forero-Torres A, Moskowitz CH, Connors JM, Engert A, Larsen EK, Kennedy DA, Sievers EL, Chen R. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol 2012; 30(18): 2183–2189
CrossRef Google scholar
[16]
Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K; EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012; 367(19): 1783–1791
CrossRef Google scholar
[17]
von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, Wolmark N, Rastogi P, Schneeweiss A, Redondo A, Fischer HH, Jacot W, Conlin AK, Arce-Salinas C, Wapnir IL, Jackisch C, DiGiovanna MP, Fasching PA, Crown JP, Wülfing P, Shao Z, Rota Caremoli E, Wu H, Lam LH, Tesarowski D, Smitt M, Douthwaite H, Singel SM, Geyer CE Jr; KATHERINE Investigators. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 2019; 380(7): 617–628
CrossRef Google scholar
[18]
Amiri-Kordestani L, Blumenthal GM, Xu QC, Zhang L, Tang SW, Ha L, Weinberg WC, Chi B, Candau-Chacon R, Hughes P, Russell AM, Miksinski SP, Chen XH, McGuinn WD, Palmby T, Schrieber SJ, Liu Q, Wang J, Song P, Mehrotra N, Skarupa L, Clouse K, Al-Hakim A, Sridhara R, Ibrahim A, Justice R, Pazdur R, Cortazar P. FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res 2014; 20(17): 4436–4441
CrossRef Google scholar
[19]
Kantarjian H, Thomas D, Jorgensen J, Jabbour E, Kebriaei P, Rytting M, York S, Ravandi F, Kwari M, Faderl S, Rios MB, Cortes J, Fayad L, Tarnai R, Wang SA, Champlin R, Advani A, O’Brien S. Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. Lancet Oncol 2012; 13(4): 403–411
CrossRef Google scholar
[20]
Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, Gökbuget N, O’Brien S, Wang K, Wang T, Paccagnella ML, Sleight B, Vandendries E, Advani AS. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med 2016; 375(8): 740–753
CrossRef Google scholar
[21]
Kreitman RJ, Dearden C, Zinzani PL, Delgado J, Karlin L, Robak T, Gladstone DE, le Coutre P, Dietrich S, Gotic M, Larratt L, Offner F, Schiller G, Swords R, Bacon L, Bocchia M, Bouabdallah K, Breems DA, Cortelezzi A, Dinner S, Doubek M, Gjertsen BT, Gobbi M, Hellmann A, Lepretre S, Maloisel F, Ravandi F, Rousselot P, Rummel M, Siddiqi T, Tadmor T, Troussard X, Yi CA, Saglio G, Roboz GJ, Balic K, Standifer N, He P, Marshall S, Wilson W, Pastan I, Yao NS, Giles F. Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia 2018; 32(8): 1768–1777
CrossRef Google scholar
[22]
Sehn LH, Herrera AF, Flowers CR, Kamdar MK, McMillan A, Hertzberg M, Assouline S, Kim TM, Kim WS, Ozcan M, Hirata J, Penuel E, Paulson JN, Cheng J, Ku G, Matasar MJ. Polatuzumab vedotin in relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol 2020; 38(2): 155–165
CrossRef Google scholar
[23]
Powles T, Rosenberg JE, Sonpavde GP, Loriot Y, Durán I, Lee JL, Matsubara N, Vulsteke C, Castellano D, Wu C, Campbell M, Matsangou M, Petrylak DP. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N Engl J Med 2021; 384(12): 1125–1135
CrossRef Google scholar
[24]
Rosenberg J, Sridhar SS, Zhang J, Smith D, Ruether D, Flaig TW, Baranda J, Lang J, Plimack ER, Sangha R, Heath EI, Merchan J, Quinn DI, Srinivas S, Milowsky M, Wu C, Gartner EM, Zuo P, Melhem-Bertrandt A, Petrylak DP. EV-101: a phase I study of single-agent enfortumab vedotin in patients with nectin-4-positive solid tumors, including metastatic urothelial carcinoma. J Clin Oncol 2020; 38(10): 1041–1049
CrossRef Google scholar
[25]
Cortés J, Kim SB, Chung WP, Im SA, Park YH, Hegg R, Kim MH, Tseng LM, Petry V, Chung CF, Iwata H, Hamilton E, Curigliano G, Xu B, Huang CS, Kim JH, Chiu JWY, Pedrini JL, Lee C, Liu Y, Cathcart J, Bako E, Verma S, Hurvitz SA; DESTINY-Breast03 Trial Investigators. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med 2022; 386(12): 1143–1154
CrossRef Google scholar
[26]
Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med 2020; 382(25): 2419–2430
CrossRef Google scholar
[27]
Yamaguchi K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Shimoyama T, Lee KW, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Shitara K. Trastuzumab deruxtecan in anti-human epidermal growth factor receptor 2 treatment-naive patients with human epidermal growth factor receptor 2-low gastric or gastroesophageal junction adenocarcinoma: exploratory cohort results in a phase II trial. J Clin Oncol 2023; 41(4): 816–825
CrossRef Google scholar
[28]
Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, Brufsky A, Sardesai SD, Kalinsky K, Zelnak AB, Weaver R, Traina T, Dalenc F, Aftimos P, Lynce F, Diab S, Cortés J, O’Shaughnessy J, Diéras V, Ferrario C, Schmid P, Carey LA, Gianni L, Piccart MJ, Loibl S, Goldenberg DM, Hong Q, Olivo MS, Itri LM, Rugo HS; ASCENT Clinical Trial Investigators. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med 2021; 384(16): 1529–1541
CrossRef Google scholar
[29]
Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, Abdallah AO, Callander N, Lendvai N, Sborov D, Suvannasankha A, Weisel K, Karlin L, Libby E, Arnulf B, Facon T, Hulin C, Kortüm KM, Rodríguez-Otero P, Usmani SZ, Hari P, Baz R, Quach H, Moreau P, Voorhees PM, Gupta I, Hoos A, Zhi E, Baron J, Piontek T, Lewis E, Jewell RC, Dettman EJ, Popat R, Esposti SD, Opalinska J, Richardson P, Cohen AD. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol 2020; 21(2): 207–221
CrossRef Google scholar
[30]
Markham A. Belantamab mafodotin: first approval. Drugs 2020; 80(15): 1607–1613
CrossRef Google scholar
[31]
Gomes-da-Silva LC, Kepp O, Kroemer G. Regulatory approval of photoimmunotherapy: photodynamic therapy that induces immunogenic cell death. OncoImmunology 2020; 9(1): 1841393
CrossRef Google scholar
[32]
Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, Kahl BS, Radford J, Solh M, Stathis A, Zinzani PL, Havenith K, Feingold J, He S, Qin Y, Ungar D, Zhang X, Carlo-Stella C. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol 2021; 22(6): 790–800
CrossRef Google scholar
[33]
Deeks ED. Disitamab vedotin: first approval. Drugs 2021; 81(16): 1929–1935
CrossRef Google scholar
[34]
Coleman RL, Lorusso D, Gennigens C, González-Martín A, Randall L, Cibula D, Lund B, Woelber L, Pignata S, Forget F, Redondo A, Vindeløv SD, Chen M, Harris JR, Smith M, Nicacio LV, Teng MSL, Laenen A, Rangwala R, Manso L, Mirza M, Monk BJ, Vergote I; innovaTV 204/GOG-3023/ENGOT-cx6 Collaborators. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol 2021; 22(5): 609–619
CrossRef Google scholar
[35]
Hong DS, Concin N, Vergote I, de Bono JS, Slomovitz BM, Drew Y, Arkenau HT, Machiels JP, Spicer JF, Jones R, Forster MD, Cornez N, Gennigens C, Johnson ML, Thistlethwaite FC, Rangwala RA, Ghatta S, Windfeld K, Harris JR, Lassen UN, Coleman RL. Tisotumab vedotin in previously treated recurrent or metastatic cervical cancer. Clin Cancer Res 2020; 26(6): 1220–1228
CrossRef Google scholar
[36]
Heo YA. Mirvetuximab soravtansine: first approval. Drugs 2023; 83(3): 265–273
CrossRef Google scholar
[37]
Nieto-Jiménez C, Sanvicente A, Díaz-Tejeiro C, Moreno V, Lopez de Sá A, Calvo E, Martínez-López J, Pérez-Segura P, Ocaña A. Uncovering therapeutic opportunities in the clinical development of antibody-drug conjugates. Clin Transl Med 2023; 13(9): e1329
CrossRef Google scholar
[38]
Maecker H, Jonnalagadda V, Bhakta S, Jammalamadaka V, Junutula JR. Exploration of the antibody-drug conjugate clinical landscape. MAbs 2023; 15(1): 2229101
CrossRef Google scholar
[39]
Weisel K, Hungria VT, Radinoff A, Delimpasi S, Mikala G, Masszi T, Li J, Capra M, Matsumoto M, Sule N, Li M, McKeown A, He W, Bright S, Currie B, Boyle J, Opalinska J, Dimopoulos MA. A phase 3, open-label, randomized study to evaluate the efficacy and safety of single-agent belantamab mafodotin (belamaf) compared to pomalidomide plus low-dose dexamethasone (Pd) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): DREAMM-3. J Clin Oncol 2023; 41(16 suppl): 8007
CrossRef Google scholar
[40]
Wolska-Washer A, Robak T. Safety and tolerability of antibody-drug conjugates in cancer. Drug Saf 2019; 42(2): 295–314
CrossRef Google scholar
[41]
Mahalingaiah PK, Ciurlionis R, Durbin KR, Yeager RL, Philip BK, Bawa B, Mantena SR, Enright BP, Liguori MJ, Van Vleet TR. Potential mechanisms of target-independent uptake and toxicity of antibody-drug conjugates. Pharmacol Ther 2019; 200: 110–125
CrossRef Google scholar
[42]
Suurs FV, Lub-de Hooge MN, de Vries EGE, de Groot DJA. A review of bispecific antibodies and antibody constructs in oncology and clinical challenges. Pharmacol Ther 2019; 201: 103–119
CrossRef Google scholar
[43]
Cavaliere A, Sun S, Lee S, Bodner J, Li Z, Huang Y, Moores SL, Marquez-Nostra B. Development of [89Zr]ZrDFO-amivantamab bispecific to EGFR and c-MET for PET imaging of triple-negative breast cancer. Eur J Nucl Med Mol Imaging 2021; 48(2): 383–394
CrossRef Google scholar
[44]
Cui X, Jia H, Xin H, Zhang L, Chen S, Xia S, Li X, Xu W, Chen X, Feng Y, Wei X, Yu H, Wang Y, Zhan Y, Zhu X, Zhang X. A novel bispecific antibody targeting PD-L1 and VEGF with combined anti-tumor activities. Front Immunol 2021; 12: 778978
CrossRef Google scholar
[45]
Neijssen J, Cardoso RMF, Chevalier KM, Wiegman L, Valerius T, Anderson GM, Moores SL, Schuurman J, Parren PWHI, Strohl WR, Chiu ML. Discovery of amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR and MET. J Biol Chem 2021; 296: 100641
CrossRef Google scholar
[46]
Wu Q, Zhen Y, Shi L, Vu P, Greninger P, Adil R, Merritt J, Egan R, Wu MJ, Yin X, Ferrone CR, Deshpande V, Baiev I, Pinto CJ, McLoughlin DE, Walmsley CS, Stone JR, Gordan JD, Zhu AX, Juric D, Goyal L, Benes CH, Bardeesy N. EGFR inhibition potentiates FGFR inhibitor therapy and overcomes resistance in FGFR2 fusion-positive cholangiocarcinoma. Cancer Discov 2022; 12(5): 1378–1395
CrossRef Google scholar
[47]
Cheng J, Liang M, Carvalho MF, Tigue N, Faggioni R, Roskos LK, Vainshtein I. Molecular mechanism of HER2 rapid internalization and redirected trafficking induced by anti-HER2 biparatopic antibody. Antibodies (Basel) 2020; 9(3): 49
CrossRef Google scholar
[48]
Dovedi SJ, Elder MJ, Yang C, Sitnikova SI, Irving L, Hansen A, Hair J, Jones DC, Hasani S, Wang B, Im SA, Tran B, Subramaniam DS, Gainer SD, Vashisht K, Lewis A, Jin X, Kentner S, Mulgrew K, Wang Y, Overstreet MG, Dodgson J, Wu Y, Palazon A, Morrow M, Rainey GJ, Browne GJ, Neal F, Murray TV, Toloczko AD, Dall’Acqua W, Achour I, Freeman DJ, Wilkinson RW, Mazor Y. Design and efficacy of a monovalent bispecific PD-1/CTLA4 antibody that enhances CTLA4 blockade on PD-1+ activated T cells. Cancer Discov 2021; 11(5): 1100–1117
CrossRef Google scholar
[49]
Wang Y, Ni H, Zhou S, He K, Gao Y, Wu W, Wu M, Wu Z, Qiu X, Zhou Y, Chen B, Pan D, Huang C, Li M, Bian Y, Yang M, Miao L, Liu J. Tumor-selective blockade of CD47 signaling with a CD47/PD-L1 bispecific antibody for enhanced anti-tumor activity and limited toxicity. Cancer Immunol Immunother 2021; 70(2): 365–376
CrossRef Google scholar
[50]
Robinson MK, Hodge KM, Horak E, Sundberg AL, Russeva M, Shaller CC, von Mehren M, Shchaveleva I, Simmons HH, Marks JD, Adams GP. Targeting ErbB2 and ErbB3 with a bispecific single-chain Fv enhances targeting selectivity and induces a therapeutic effect in vitro. Br J Cancer 2008; 99(9): 1415–1425
CrossRef Google scholar
[51]
Zhao H, Luo F, Xue J, Li S, Xu RH. Emerging immunological strategies: recent advances and future directions. Front Med 2021; 15(6): 805–828
CrossRef Google scholar
[52]
Frampton JE. Catumaxomab: in malignant ascites. Drugs 2012; 72(10): 1399–1410
CrossRef Google scholar
[53]
Kantarjian H, Stein A, Gökbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A, Dombret H, Foà R, Bassan R, Arslan Ö, Sanz MA, Bergeron J, Demirkan F, Lech-Maranda E, Rambaldi A, Thomas X, Horst HA, Brüggemann M, Klapper W, Wood BL, Fleishman A, Nagorsen D, Holland C, Zimmerman Z, Topp MS. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med 2017; 376(9): 836–847
CrossRef Google scholar
[54]
Oldenburg J, Mahlangu JN, Kim B, Schmitt C, Callaghan MU, Young G, Santagostino E, Kruse-Jarres R, Negrier C, Kessler C, Valente N, Asikanius E, Levy GG, Windyga J, Shima M. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med 2017; 377(9): 809–818
CrossRef Google scholar
[55]
Zhou C, Tang KJ, Cho BC, Liu B, Paz-Ares L, Cheng S, Kitazono S, Thiagarajan M, Goldman JW, Sabari JK, Sanborn RE, Mansfield AS, Hung JY, Boyer M, Popat S, Mourão Dias J, Felip E, Majem M, Gumus M, Kim SW, Ono A, Xie J, Bhattacharya A, Agrawal T, Shreeve SM, Knoblauch RE, Park K, Girard N; PAPILLON Investigators. Amivantamab plus chemotherapy in NSCLC with EGFR exon 20 insertions. N Engl J Med 2023; 389(22): 2039–2051
CrossRef Google scholar
[56]
Nathan P, Hassel JC, Rutkowski P, Baurain JF, Butler MO, Schlaak M, Sullivan RJ, Ochsenreither S, Dummer R, Kirkwood JM, Joshua AM, Sacco JJ, Shoushtari AN, Orloff M, Piulats JM, Milhem M, Salama AKS, Curti B, Demidov L, Gastaud L, Mauch C, Yushak M, Carvajal RD, Hamid O, Abdullah SE, Holland C, Goodall H, Piperno-Neumann S; IMCgp100-202 Investigators. Overall survival benefit with tebentafusp in metastatic uveal melanoma. N Engl J Med 2021; 385(13): 1196–1206
CrossRef Google scholar
[57]
Heier JS, Khanani AM, Quezada Ruiz C, Basu K, Ferrone PJ, Brittain C, Figueroa MS, Lin H, Holz FG, Patel V, Lai TYY, Silverman D, Regillo C, Swaminathan B, Viola F, Cheung CMG, Wong TY; TENAYA, LUCERNE Investigators. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials. Lancet 2022; 399(10326): 729–740
CrossRef Google scholar
[58]
Wykoff CC, Abreu F, Adamis AP, Basu K, Eichenbaum DA, Haskova Z, Lin H, Loewenstein A, Mohan S, Pearce IA, Sakamoto T, Schlottmann PG, Silverman D, Sun JK, Wells JA, Willis JR, Tadayoni R; YOSEMITE, RHINE Investigators. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials. Lancet 2022; 399(10326): 741–755
CrossRef Google scholar
[59]
Budde LE, Sehn LH, Matasar M, Schuster SJ, Assouline S, Giri P, Kuruvilla J, Canales M, Dietrich S, Fay K, Ku M, Nastoupil L, Cheah CY, Wei MC, Yin S, Li CC, Huang H, Kwan A, Penuel E, Bartlett NL. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Lancet Oncol 2022; 23(8): 1055–1065
CrossRef Google scholar
[60]
Keam SJ. Cadonilimab: first approval. Drugs 2022; 82(12): 1333–1339
CrossRef Google scholar
[61]
Moreau P, Garfall AL, van de Donk NWCJ, Nahi H, San-Miguel JF, Oriol A, Nooka AK, Martin T, Rosinol L, Chari A, Karlin L, Benboubker L, Mateos MV, Bahlis N, Popat R, Besemer B, Martínez-López J, Sidana S, Delforge M, Pei L, Trancucci D, Verona R, Girgis S, Lin SXW, Olyslager Y, Jaffe M, Uhlar C, Stephenson T, Van Rampelbergh R, Banerjee A, Goldberg JD, Kobos R, Krishnan A, Usmani SZ. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med 2022; 387(6): 495–505
CrossRef Google scholar
[62]
Takeuchi T, Kawanishi M, Nakanishi M, Yamasaki H, Tanaka Y. Phase II/III results of a trial of anti-tumor necrosis factor multivalent NANOBODY compound ozoralizumab in patients with rheumatoid arthritis. Arthritis Rheumatol 2022; 74(11): 1776–1785
CrossRef Google scholar
[63]
Thieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, Do YR, Feldman T, Gasiorowski R, Jurczak W, Kim TM, Lewis DJ, van der Poel M, Poon ML, Cota Stirner M, Kilavuz N, Chiu C, Chen M, Sacchi M, Elliott B, Ahmadi T, Hutchings M, Lugtenburg PJ. Epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell-engaging antibody, in relapsed or refractory large B-cell lymphoma: dose expansion in a phase I/II trial. J Clin Oncol 2023; 41(12): 2238–2247
CrossRef Google scholar
[64]
Dickinson MJ, Carlo-Stella C, Morschhauser F, Bachy E, Corradini P, Iacoboni G, Khan C, Wróbel T, Offner F, Trněný M, Wu SJ, Cartron G, Hertzberg M, Sureda A, Perez-Callejo D, Lundberg L, Relf J, Dixon M, Clark E, Humphrey K, Hutchings M. Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med 2022; 387(24): 2220–2231
CrossRef Google scholar
[65]
Lesokhin AM, Tomasson MH, Arnulf B, Bahlis NJ, Miles Prince H, Niesvizky R, Rodrίguez-Otero P, Martinez-Lopez J, Koehne G, Touzeau C, Jethava Y, Quach H, Depaus J, Yokoyama H, Gabayan AE, Stevens DA, Nooka AK, Manier S, Raje N, Iida S, Raab MS, Searle E, Leip E, Sullivan ST, Conte U, Elmeliegy M, Czibere A, Viqueira A, Mohty M. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med 2023; 29(9): 2259–2267
CrossRef Google scholar
[66]
Chari A, Minnema MC, Berdeja JG, Oriol A, van de Donk NWCJ, Rodríguez-Otero P, Askari E, Mateos MV, Costa LJ, Caers J, Verona R, Girgis S, Yang S, Goldsmith RB, Yao X, Pillarisetti K, Hilder BW, Russell J, Goldberg JD, Krishnan A. Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma. N Engl J Med 2022; 387(24): 2232–2244
CrossRef Google scholar
[67]
Labrijn AF, Janmaat ML, Reichert JM, Parren PWHI. Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov 2019; 18(8): 585–608
CrossRef Google scholar
[68]
Khaw BA, Gada KS, Patil V, Panwar R, Mandapati S, Hatefi A, Majewski S, Weisenberger A. Bispecific antibody complex pre-targeting and targeted delivery of polymer drug conjugates for imaging and therapy in dual human mammary cancer xenografts: targeted polymer drug conjugates for cancer diagnosis and therapy. Eur J Nucl Med Mol Imaging 2014; 41(8): 1603–1616
CrossRef Google scholar
[69]
Sharkey RM, van Rij CM, Karacay H, Rossi EA, Frielink C, Regino C, Cardillo TM, McBride WJ, Chang CH, Boerman OC, Goldenberg DM. A new Tri-Fab bispecific antibody for pretargeting Trop-2-expressing epithelial cancers. J Nucl Med 2012; 53(10): 1625–1632
CrossRef Google scholar
[70]
Brinkmann U, Kontermann RE. The making of bispecific antibodies. MAbs 2017; 9(2): 182–212
CrossRef Google scholar
[71]
Ridgway JBB, Presta LG, Carter P. ‘Knobs-into-holes’ engineering of antibody CH3 domains for heavy chain heterodimerization. Protein Eng 1996; 9(7): 617–621
CrossRef Google scholar
[72]
Davis JH, Aperlo C, Li Y, Kurosawa E, Lan Y, Lo KM, Huston JS. SEEDbodies: fusion proteins based on strand-exchange engineered domain (SEED) CH3 heterodimers in an Fc analogue platform for asymmetric binders or immunofusions and bispecific antibodies. Protein Eng Des Sel 2010; 23(4): 195–202
CrossRef Google scholar
[73]
Rossi EA, Goldenberg DM, Chang CH. The dock-and-lock method combines recombinant engineering with site-specific covalent conjugation to generate multifunctional structures. Bioconjug Chem 2012; 23(3): 309–323
CrossRef Google scholar
[74]
Shim H. Bispecific antibodies and antibody-drug conjugates for cancer therapy: technological considerations. Biomolecules 2020; 10(3): 360
CrossRef Google scholar
[75]
Khongorzul P, Ling CJ, Khan FU, Ihsan AU, Zhang J. Antibody-drug conjugates: a comprehensive review. Mol Cancer Res 2020; 18(1): 3–19
CrossRef Google scholar
[76]
Li B, Meng Y, Zheng L, Zhang X, Tong Q, Tan W, Hu S, Li H, Chen Y, Song J, Zhang G, Zhao L, Zhang D, Hou S, Qian W, Guo Y. Bispecific antibody to ErbB2 overcomes trastuzumab resistance through comprehensive blockade of ErbB2 heterodimerization. Cancer Res 2013; 73(21): 6471–6483
CrossRef Google scholar
[77]
Castoldi R, Ecker V, Wiehle L, Majety M, Busl-Schuller R, Asmussen M, Nopora A, Jucknischke U, Osl F, Kobold S, Scheuer W, Venturi M, Klein C, Niederfellner G, Sustmann C. A novel bispecific EGFR/Met antibody blocks tumor-promoting phenotypic effects induced by resistance to EGFR inhibition and has potent antitumor activity. Oncogene 2013; 32(50): 5593–5601
CrossRef Google scholar
[78]
Kim YJ, Baek DS, Lee S, Park D, Kang HN, Cho BC, Kim YS. Dual-targeting of EGFR and neuropilin-1 attenuates resistance to EGFR-targeted antibody therapy in KRAS-mutant non-small cell lung cancer. Cancer Lett 2019; 466: 23–34
CrossRef Google scholar
[79]
Nguyen TD, Bordeau BM, Balthasar JP. Mechanisms of ADC toxicity and strategies to increase ADC tolerability. Cancers (Basel) 2023; 15(3): 713
CrossRef Google scholar
[80]
Maruani A. Bispecifics and antibody-drug conjugates: a positive synergy. Drug Discov Today Technol 2018; 30: 55–61
CrossRef Google scholar
[81]
Bargh JD, Isidro-Llobet A, Parker JS, Spring DR. Cleavable linkers in antibody-drug conjugates. Chem Soc Rev 2019; 48(16): 4361–4374
CrossRef Google scholar
[82]
Coleman N, Yap TA, Heymach JV, Meric-Bernstam F, Le X. Antibody-drug conjugates in lung cancer: dawn of a new era. NPJ Precis Oncol 2023; 7(1): 5
CrossRef Google scholar
[83]
Ogitani Y, Hagihara K, Oitate M, Naito H, Agatsuma T. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Sci 2016; 107(7): 1039–1046
CrossRef Google scholar
[84]
Giugliano F, Corti C, Tarantino P, Michelini F, Curigliano G. Bystander effect of antibody-drug conjugates: fact or fiction. Curr Oncol Rep 2022; 24(7): 809–817
CrossRef Google scholar
[85]
Kovtun YV, Audette CA, Ye Y, Xie H, Ruberti MF, Phinney SJ, Leece BA, Chittenden T, Blättler WA, Goldmacher VS. Antibody-drug conjugates designed to eradicate tumors with homogeneous and heterogeneous expression of the target antigen. Cancer Res 2006; 66(6): 3214–3221
CrossRef Google scholar
[86]
Pronk SD, Schooten E, Heinen J, Helfrich E, Oliveira S, van Bergen en Henegouwen PMP. Single domain antibodies as carriers for intracellular drug delivery: a proof of principle study. Biomolecules 2021; 11(7): 927
CrossRef Google scholar
[87]
Xu S. Internalization, trafficking, intracellular processing and actions of antibody-drug conjugates. Pharm Res 2015; 32(11): 3577–3583
CrossRef Google scholar
[88]
Kelton C, Wesolowski JS, Soloviev M, Schweickhardt R, Fischer D, Kurosawa E, McKenna SD, Gross AW. Anti-EGFR biparatopic-SEED antibody has enhanced combination-activity in a single molecule. Arch Biochem Biophys 2012; 526(2): 219–225
CrossRef Google scholar
[89]
Friedman LM, Rinon A, Schechter B, Lyass L, Lavi S, Bacus SS, Sela M, Yarden Y. Synergistic down-regulation of receptor tyrosine kinases by combinations of mAbs: implications for cancer immunotherapy. Proc Natl Acad Sci USA 2005; 102(6): 1915–1920
CrossRef Google scholar
[90]
Spangler JB, Neil JR, Abramovitch S, Yarden Y, White FM, Lauffenburger DA, Wittrup KD. Combination antibody treatment down-regulates epidermal growth factor receptor by inhibiting endosomal recycling. Proc Natl Acad Sci USA 2010; 107(30): 13252–13257
CrossRef Google scholar
[91]
ComerFGao CCoatsS. Bispecific and biparatopic antibody drug conjugates. In: Damelin M. Innovations for Next-Generation Antibody-Drug Conjugates. Cham: Springer International Publishing, 2018: 267–280
[92]
Hunter FW, Barker HR, Lipert B, Rothé F, Gebhart G, Piccart-Gebhart MJ, Sotiriou C, Jamieson SMF. Mechanisms of resistance to trastuzumab emtansine (T-DM1) in HER2-positive breast cancer. Br J Cancer 2020; 122(5): 603–612
CrossRef Google scholar
[93]
Pegram MD, Miles D, Tsui CK, Zong Y. HER2-overexpressing/amplified breast cancer as a testing ground for antibody-drug conjugate drug development in solid tumors. Clin Cancer Res 2020; 26(4): 775–786
CrossRef Google scholar
[94]
Weisser NE, Sanches M, Escobar-Cabrera E, O’Toole J, Whalen E, Chan PWY, Wickman G, Abraham L, Choi K, Harbourne B, Samiotakis A, Rojas AH, Volkers G, Wong J, Atkinson CE, Baardsnes J, Worrall LJ, Browman D, Smith EE, Baichoo P, Cheng CW, Guedia J, Kang S, Mukhopadhyay A, Newhook L, Ohrn A, Raghunatha P, Zago-Schmitt M, Schrag JD, Smith J, Zwierzchowski P, Scurll JM, Fung V, Black S, Strynadka NCJ, Gold MR, Presta LG, Ng G, Dixit S. An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity. Nat Commun 2023; 14(1): 1394
CrossRef Google scholar
[95]
Harding JJ, Fan J, Oh DY, Choi HJ, Kim JW, Chang HM, Bao L, Sun HC, Macarulla T, Xie F, Metges JP, Ying J, Bridgewater J, Lee MA, Tejani MA, Chen EY, Kim DU, Wasan H, Ducreux M, Bao Y, Boyken L, Ma J, Garfin P, Pant S; HERIZON-BTC-01 study group. Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study. Lancet Oncol 2023; 24(7): 772–782
CrossRef Google scholar
[96]
De Santis R. Anti-ErbB2 immunotherapeutics: struggling to make better antibodies for cancer therapy. MAbs 2020; 12(1): 1725346
CrossRef Google scholar
[97]
Huang S, Li F, Liu H, Ye P, Fan X, Yuan X, Wu Z, Chen J, Jin C, Shen B, Feng J, Zhang B. Structural and functional characterization of MBS301, an afucosylated bispecific anti-HER2 antibody. MAbs 2018; 10(6): 864–875
CrossRef Google scholar
[98]
Lee NK, Su Y, Bidlingmaier S, Liu B. Manipulation of cell-type selective antibody internalization by a guide-effector bispecific design. Mol Cancer Ther 2019; 18(6): 1092–1103
CrossRef Google scholar
[99]
de Goeij BE, Vink T, Ten Napel H, Breij EC, Satijn D, Wubbolts R, Miao D, Parren PW. Efficient payload delivery by a bispecific antibody-drug conjugate targeting HER2 and CD63. Mol Cancer Ther 2016; 15(11): 2688–2697
CrossRef Google scholar
[100]
Pols MS, Klumperman J. Trafficking and function of the tetraspanin CD63. Exp Cell Res 2009; 315(9): 1584–1592
CrossRef Google scholar
[101]
DeVay RM, Delaria K, Zhu G, Holz C, Foletti D, Sutton J, Bolton G, Dushin R, Bee C, Pons J, Rajpal A, Liang H, Shelton D, Liu SH, Strop P. Improved lysosomal trafficking can modulate the potency of antibody drug conjugates. Bioconjug Chem 2017; 28(4): 1102–1114
CrossRef Google scholar
[102]
Rupp U, Schoendorf-Holland E, Eichbaum M, Schuetz F, Lauschner I, Schmidt P, Staab A, Hanft G, Huober J, Sinn HP, Sohn C, Schneeweiss A. Safety and pharmacokinetics of bivatuzumab mertansine in patients with CD44v6-positive metastatic breast cancer: final results of a phase I study. Anticancer Drugs 2007; 18(4): 477–485
CrossRef Google scholar
[103]
Rosenberg JE, O’Donnell PH, Balar AV, McGregor BA, Heath EI, Yu EY, Galsky MD, Hahn NM, Gartner EM, Pinelli JM, Liang SY, Melhem-Bertrandt A, Petrylak DP. Pivotal trial of enfortumab vedotin in urothelial carcinoma after platinum and anti-programmed death 1/programmed death ligand 1 therapy. J Clin Oncol 2019; 37(29): 2592–2600
CrossRef Google scholar
[104]
Saleh MN, Sugarman S, Murray J, Ostroff JB, Healey D, Jones D, Daniel CR, LeBherz D, Brewer H, Onetto N, LoBuglio AF. Phase I trial of the anti-Lewis Y drug immunoconjugate BR96-doxorubicin in patients with lewis Y-expressing epithelial tumors. J Clin Oncol 2000; 18(11): 2282–2292
CrossRef Google scholar
[105]
Dheilly E, Moine V, Broyer L, Salgado-Pires S, Johnson Z, Papaioannou A, Cons L, Calloud S, Majocchi S, Nelson R, Rousseau F, Ferlin W, Kosco-Vilbois M, Fischer N, Masternak K. Selective blockade of the ubiquitous checkpoint receptor CD47 is enabled by dual-targeting bispecific antibodies. Mol Ther 2017; 25(2): 523–533
CrossRef Google scholar
[106]
Baruch A, Wong C, Chinn LW, Vaze A, Sonoda J, Gelzleichter T, Chen S, Lewin-Koh N, Morrow L, Dheerendra S, Boismenu R, Gutierrez J, Wakshull E, Wilson ME, Arora PS. Antibody-mediated activation of the FGFR1/Klothoβ complex corrects metabolic dysfunction and alters food preference in obese humans. Proc Natl Acad Sci USA 2020; 117(46): 28992–29000
CrossRef Google scholar
[107]
Geng L, Lam KSL, Xu A. The therapeutic potential of FGF21 in metabolic diseases: from bench to clinic. Nat Rev Endocrinol 2020; 16(11): 654–667
CrossRef Google scholar
[108]
Liu S, Lyu W, Yin S, Lei Y, Zhuo Q, Zheng L, Sun B, Tan S, Jiang L, Zhang T, Gao B, Xu R, Huang D, Li Y, Wu Z, Wu D, Wen Y. Abstract 6307: a novel pegylated bispecific antibody-drug conjugate (P-BsADCpb-adc) targeting cancers co-expressing PD-L1 and CD47. Cancer Res 2023; 83(7 Supplement): 6307
CrossRef Google scholar
[109]
Baas JM, Krens LL, Guchelaar HJ, Ouwerkerk J, de Jong FA, Lavrijsen AP, Gelderblom H. Recommendations on management of EGFR inhibitor-induced skin toxicity: a systematic review. Cancer Treat Rev 2012; 38(5): 505–514
CrossRef Google scholar
[110]
Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer 2006; 6(10): 803–812
CrossRef Google scholar
[111]
Knuehl C, Toleikis L, Dotterweich J, Ma J, Kumar S, Ross E, Wilm C, Schmitt M, Grote HJ, Amendt C. Abstract 5284: M1231 is a bispecific anti-MUC1xEGFR antibody-drug conjugate designed to treat solid tumors with MUC1 and EGFR co-expression. Cancer Res 2022; 82(12 Supplement): 5284
CrossRef Google scholar
[112]
Ma Y, Huang Y, Zhao Y, Zhao S, Xue J, Yang Y, Fang W, Guo Y, Han Y, Yang K, Li Y, Yang J, Fu Z, Chen G, Chen L, Zhou N, Zhou T, Zhang Y, Zhou H, Liu Q, Zhu Y, Zhu H, Xiao S, Zhang L, Zhao H. BL-B01D1, a first-in-class EGFR-HER3 bispecific antibody-drug conjugate, in patients with locally advanced or metastatic solid tumours: a first-in-human, open-label, multicentre, phase 1 study. Lancet Oncol 2024; 29: S1470–2045(24)00159–1
CrossRef Google scholar
[113]
McGrath L, Zheng Y, Christ S, Sachs CC, Khelifa S, Windmüller C, Sweet S, Kim YJ, Sutton D, Sulikowski M, Lewis A, Inigo I, Floch N, Rosfjord E, Arnaldez F, Comer F. Abstract 5737: Evaluation of the relationship between target expression and in vivo anti-tumor efficacy of AZD9592, an EGFR/c-MET targeted bispecific antibody drug conjugate. Cancer Res 2023; 83(7 Supplement): 5737
CrossRef Google scholar
[114]
Khoury R, Saleh K, Khalife N, Saleh M, Chahine C, Ibrahim R, Lecesne A. Mechanisms of resistance to antibody-drug conjugates. Int J Mol Sci 2023; 24(11): 9674
CrossRef Google scholar
[115]
Díaz-Rodríguez E, Gandullo-Sánchez L, Ocaña A, Pandiella A. Novel ADCs and strategies to overcome resistance to anti-HER2 ADCs. Cancers (Basel) 2021; 14(1): 154
CrossRef Google scholar
[116]
Ab O, Bartle LM, Lanieri L, Ponte JF, Qiu QF, Sikka S, Costoplus JA, Deats W, Yoder NC, Widdison WC, Mucciarone K, Selvitelli K, Chen Y, Kohli N, Chittenden T, Gregory R, Setiady Y, Westin EH. IMGN151-A next generation folate receptor alpha targeting antibody drug conjugate active against tumors with low, medium and high receptor expression. Cancer Res 2020; 80(16 Supplement): 2890
CrossRef Google scholar
[117]
DaSilva JO, Yang K, Perez Bay AE, Andreev J, Ngoi P, Pyles E, Franklin MC, Dudgeon D, Rafique A, Dore A, Delfino FJ, Potocky TB, Babb R, Chen G, MacDonald D, Olson WC, Thurston G, Daly C. A biparatopic antibody that modulates MET trafficking exhibits enhanced efficacy compared with parental antibodies in MET-driven tumor models. Clin Cancer Res 2020; 26(6): 1408–1419
CrossRef Google scholar
[118]
Filho OM, Viale G, Stein S, Trippa L, Yardley DA, Mayer IA, Abramson VG, Arteaga CL, Spring LM, Waks AG, Wrabel E, DeMeo MK, Bardia A, Dell’Orto P, Russo L, King TA, Polyak K, Michor F, Winer EP, Krop IE. Impact of HER2 heterogeneity on treatment response of early-stage HER2-positive breast cancer: phase II neoadjuvant clinical trial of T-DM1 combined with pertuzumab. Cancer Discov 2021; 11(10): 2474–2487
CrossRef Google scholar
[119]
Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol 2021; 32(6): 757–765
CrossRef Google scholar
[120]
Fan J, Zhuang X, Yang X, Xu Y, Zhou Z, Pan L, Chen S. A multivalent biparatopic EGFR-targeting nanobody drug conjugate displays potent anticancer activity in solid tumor models. Signal Transduct Target Ther 2021; 6(1): 320
CrossRef Google scholar
[121]
Larsen MT, Kuhlmann M, Hvam ML, Howard KA. Albumin-based drug delivery: harnessing nature to cure disease. Mol Cell Ther 2016; 4(1): 3
CrossRef Google scholar
[122]
Dennis MS, Jin H, Dugger D, Yang R, McFarland L, Ogasawara A, Williams S, Cole MJ, Ross S, Schwall R. Imaging tumors with an albumin-binding Fab, a novel tumor-targeting agent. Cancer Res 2007; 67(1): 254–261
CrossRef Google scholar
[123]
Li Q, Barrett A, Vijayakrishnan B, Tiberghien A, Beard R, Rickert KW, Allen KL, Christie RJ, Marelli M, Harper J, Howard P, Wu H, Dall’Acqua WF, Tsui P, Gao C, Borrok MJ. Improved inhibition of tumor growth by diabody-drug conjugates via half-life extension. Bioconjug Chem 2019; 30(4): 1232–1243
CrossRef Google scholar
[124]
Han Z, Shang C, Dai W, An G, Zhang E, Lin Q, Yang Y. Abstract LB213: Identification of DM004, a first-in-class anti-5T4/MET bispecific antibody-drug conjugate. Cancer Res 2023; 83(8 Supplement): LB213
CrossRef Google scholar
[125]
Li Z, Shang C, Guan X, An G, Guo Y, Zhang E, Lin Q, Yang Y. Abstract LB215: A first-in-class anti-TROP2/EGFR bispecific antibody-drug conjugate, DM001, exhibits potent anti-tumor efficacy. Cancer Res 2023; 83(8 Supplement): LB215
CrossRef Google scholar
[126]
Li Z, Shang C, Guan X, Han Z, An G, Zhang E, Lin Q, Yang Y. Abstract LB212: BCG022: A novel bispecific antibody-drug conjugate targeting HER3 and MET. Cancer Res 2023; 83(8 Supplement): LB212
CrossRef Google scholar
[127]
Shang C, An G, Guo Y, Zhang E, Lin Q, Yang Y. Abstract 2977: A first-in-class anti-HER2/TROP2 bispecific antibody-drug conjugate (YH012) exhibits potent anti-tumor efficacy. Cancer Res 2023; 83(7 Supplement): 2977
CrossRef Google scholar
[128]
Yao S, Shang C, An G, Zhang E, Lin Q, Yang Y. Abstract LB216: Discovery of BCG033, a novel anti-PTK7 x TROP2 bispecific antibody-drug conjugate with promising efficacy against triple-negative breast cancer. Cancer Res 2023; 83(8 Supplement): LB216
CrossRef Google scholar
[129]
Zhang Y, Shang C, Wang N, An G, Zhang E, Lin Q, Yang Y. Abstract LB214: A first-in-class bispecific antibody-drug conjugate (DM002) targeting HER3 and the juxtamembrane domain of MUC1. Cancer Res 2023; 83(8 Supplement): LB214
CrossRef Google scholar
[130]
Jiménez-Labaig P, Rullan A, Hernando-Calvo A, Llop S, Bhide S, O'Leary B, Braña I, Harrington KJ. A systematic review of antibody-drug conjugates and bispecific antibodies in head and neck squamous cell carcinoma and nasopha-ryngeal carcinoma: Charting the course of future therapies. Cancer Treat Rev 2024; 128: 102772
CrossRef Google scholar
[131]
Haikala HM, Jänne PA. Thirty years of HER3: from basic biology to therapeutic interventions. Clin Cancer Res 2021; 27(13): 3528–3539
CrossRef Google scholar
[132]
Uliano J, Corvaja C, Curigliano G, Tarantino P. Targeting HER3 for cancer treatment: a new horizon for an old target. ESMO Open 2023; 8(1): 100790
CrossRef Google scholar
[133]
Matsumoto K, Nakamura T. Hepatocyte growth factor and the Met system as a mediator of tumor-stromal interactions. Int J Cancer 2006; 119(3): 477–483
CrossRef Google scholar
[134]
Matsumoto K, Umitsu M, De Silva DM, Roy A, Bottaro DP. Hepatocyte growth factor/MET in cancer progression and biomarker discovery. Cancer Sci 2017; 108(3): 296–307
CrossRef Google scholar
[135]
Dulak AM, Gubish CT, Stabile LP, Henry C, Siegfried JM. HGF-independent potentiation of EGFR action by c-Met. Oncogene 2011; 30(33): 3625–3635
CrossRef Google scholar
[136]
Sequist LV, Han JY, Ahn MJ, Cho BC, Yu H, Kim SW, Yang JC, Lee JS, Su WC, Kowalski D, Orlov S, Cantarini M, Verheijen RB, Mellemgaard A, Ottesen L, Frewer P, Ou X, Oxnard G. Osimertinib plus savolitinib in patients with EGFR mutation-positive, MET-amplified, non-small-cell lung cancer after progression on EGFR tyrosine kinase inhibitors: interim results from a multicentre, open-label, phase 1b study. Lancet Oncol 2020; 21(3): 373–386
CrossRef Google scholar
[137]
Ou SI, Young L, Schrock AB, Johnson A, Klempner SJ, Zhu VW, Miller VA, Ali SM. Emergence of preexisting MET Y1230C mutation as a resistance mechanism to crizotinib in NSCLC with MET exon 14 skipping. J Thorac Oncol 2017; 12(1): 137–140
CrossRef Google scholar
[138]
Lai GGY, Lim TH, Lim J, Liew PJR, Kwang XL, Nahar R, Aung ZW, Takano A, Lee YY, Lau DPX, Tan GS, Tan SH, Tan WL, Ang MK, Toh CK, Tan BS, Devanand A, Too CW, Gogna A, Ong BH, Koh TPT, Kanesvaran R, Ng QS, Jain A, Rajasekaran T, Yuan J, Lim TKH, Lim AST, Hillmer AM, Lim WT, Iyer NG, Tam WL, Zhai W, Tan EH, Tan DSW. Clonal MET amplification as a determinant of tyrosine kinase inhibitor resistance in epidermal growth factor receptor-mutant non-small-cell lung cancer. J Clin Oncol 2019; 37(11): 876–884
CrossRef Google scholar
[139]
Baldacci S, Kherrouche Z, Cockenpot V, Stoven L, Copin MC, Werkmeister E, Marchand N, Kyheng M, Tulasne D, Cortot AB. MET amplification increases the metastatic spread of EGFR-mutated NSCLC. Lung Cancer 2018; 125: 57–67
CrossRef Google scholar
[140]
Oh SY, Lee YW, Lee EJ, Kim JH, Park Y, Heo SG, Yu MR, Hong MH, DaSilva J, Daly C, Cho BC, Lim SM, Yun MR. Preclinical study of a biparatopic METxMET antibody-drug conjugate, REGN5093-M114, overcomes MET-driven acquired resistance to EGFR TKIs in EGFR-mutant NSCLC. Clin Cancer Res 2023; 29(1): 221–232
CrossRef Google scholar
[141]
DaSilva JO, Yang K, Surriga O, Nittoli T, Kunz A, Franklin MC, Delfino FJ, Mao S, Zhao F, Giurleo JT, Kelly MP, Makonnen S, Hickey C, Krueger P, Foster R, Chen Z, Retter MW, Slim R, Young TM, Olson WC, Thurston G, Daly C. A biparatopic antibody-drug conjugate to treat MET-expressing cancers, including those that are unresponsive to MET pathway blockade. Mol Cancer Ther 2021; 20(10): 1966–1976
CrossRef Google scholar
[142]
Perez Bay AE, Faulkner D, DaSilva JO, Young TM, Yang K, Giurleo JT, Ma D, Delfino FJ, Olson WC, Thurston G, Daly C, Andreev J. A bispecific METxMET antibody-drug conjugate with cleavable linker is processed in recycling and late endosomes. Mol Cancer Ther 2023; 22(3): 357–370
CrossRef Google scholar
[143]
Li JY, Perry SR, Muniz-Medina V, Wang X, Wetzel LK, Rebelatto MC, Hinrichs MJ, Bezabeh BZ, Fleming RL, Dimasi N, Feng H, Toader D, Yuan AQ, Xu L, Lin J, Gao C, Wu H, Dixit R, Osbourn JK, Coats SR. A biparatopic HER2-targeting antibody-drug conjugate induces tumor regression in primary models refractory to or ineligible for HER2-targeted therapy. Cancer Cell 2016; 29(1): 117–129
CrossRef Google scholar
[144]
HamblettKBarnscher SDaviesRHammondPHernandez AWickmanGFungVDingT GarnettGGaley AZwierzchowskiPClavetteBWintersG RichJRowse GBabcookJHausmanD. Abstract P6–17–13: ZW49, a HER2 targeted biparatopic antibody drug conjugate for the treatment of HER2 expressing cancers. Cancer Res 2019; 79(4_Supplement): P6–17–13
[145]
Pegram MD, Hamilton EP, Tan AR, Storniolo AM, Balic K, Rosenbaum AI, Liang M, He P, Marshall S, Scheuber A, Das M, Patel MR. First-in-human, phase 1 dose-escalation study of biparatopic anti-HER2 antibody-drug conjugate MEDI4276 in patients with HER2-positive advanced breast or gastric cancer. Mol Cancer Ther 2021; 20(8): 1442–1453
CrossRef Google scholar
[146]
Jhaveri K, Han H, Dotan E, Oh DY, Ferrario C, Tolcher A, Lee KW, Liao CY, Kang YK, Kim YH, Hamilton E, Spira A, Patel N, Karapetis C, Rha SY, Boyken L, Woolery J, Bedard P. Preliminary results from a phase I study using the bispecific, human epidermal growth factor 2 (HER2)-targeting antibody-drug conjugate (ADC) zanidatamab zovodotin (ZW49) in solid cancers. Ann Oncol 2022; 33(7): S749–S750
CrossRef Google scholar
[147]
Hinrichs MJ, Dixit R. Antibody drug conjugates: nonclinical safety considerations. AAPS J 2015; 17(5): 1055–1064
CrossRef Google scholar
[148]
Gu Y, Wang Z, Wang Y. Bispecific antibody drug conjugates: Making 1+1 > 2. Acta Pharm Sin B. 2024; 14(5): 1965–1986
CrossRef Google scholar
[149]
Wang P, Guo K, Peng J, Sun J, Xu T. JSKN003, a novel biparatopic anti-HER2 antibody-drug conjugate, exhibits potent antitumor efficacy. Antib Ther 2023; 6: tbad014.009
CrossRef Google scholar
[150]
Kharbanda A, Rajabi H, Jin C, Tchaicha J, Kikuchi E, Wong KK, Kufe D. Targeting the oncogenic MUC1-C protein inhibits mutant EGFR-mediated signaling and survival in non-small cell lung cancer cells. Clin Cancer Res 2014; 20(21): 5423–5434
CrossRef Google scholar
[151]
Piyush T, Chacko AR, Sindrewicz P, Hilkens J, Rhodes JM, Yu LG. Interaction of galectin-3 with MUC1 on cell surface promotes EGFR dimerization and activation in human epithelial cancer cells. Cell Death Differ 2017; 24(11): 1937–1947
CrossRef Google scholar
[152]
Davis JH, Aperlo C, Li Y, Kurosawa E, Lan Y, Lo KM, Huston JS. SEEDbodies: fusion proteins based on strand-exchange engineered domain (SEED) CH3 heterodimers in an Fc analogue platform for asymmetric binders or immunofusions and bispecific antibodies. Protein Eng Des Sel 2010; 23(4): 195–202
CrossRef Google scholar
[153]
Zhang Y, Shang C, Wang A, Zhang J, Liu Y, Li H, Li X, An G, Hui L, An F, Yang Y. Abstract 6325: A novel EGFR x MUC1 bispecific antibody-drug conjugate, BSA01, targets MUC1 transmembrane cleavage products and improves tumor selectivity. Cancer Res 2023; 83(7 Supplement): 6325
CrossRef Google scholar
[154]
Dong Q, Du Y, Li H, Liu C, Wei Y, Chen MK, Zhao X, Chu YY, Qiu Y, Qin L, Yamaguchi H, Hung MC. EGFR and c-MET cooperate to enhance resistance to PARP inhibitors in hepatocellular carcinoma. Cancer Res 2019; 79(4): 819–829
CrossRef Google scholar
[155]
Wu YL, Soo RA, Locatelli G, Stammberger U, Scagliotti G, Park K. Does c-Met remain a rational target for therapy in patients with EGFR TKI-resistant non-small cell lung cancer. Cancer Treat Rev 2017; 61: 70–81
CrossRef Google scholar
[156]
Huang L, Fu L. Mechanisms of resistance to EGFR tyrosine kinase inhibitors. Acta Pharm Sin B 2015; 5(5): 390–401
CrossRef Google scholar
[157]
Moores SL, Chiu ML, Bushey BS, Chevalier K, Luistro L, Dorn K, Brezski RJ, Haytko P, Kelly T, Wu SJ, Martin PL, Neijssen J, Parren PW, Schuurman J, Attar RM, Laquerre S, Lorenzi MV, Anderson GM. A novel bispecific antibody targeting EGFR and cMet is effective against EGFR inhibitor-resistant lung tumors. Cancer Res 2016; 76(13): 3942–3953
CrossRef Google scholar
[158]
Wu DW, Chen TC, Huang HS, Lee H. TC-N19, a novel dual inhibitor of EGFR and cMET, efficiently overcomes EGFR-TKI resistance in non-small-cell lung cancer cells. Cell Death Dis 2016; 7(6): e2290
CrossRef Google scholar
[159]
Wu YL, Zhang L, Kim DW, Liu X, Lee DH, Yang JC, Ahn MJ, Vansteenkiste JF, Su WC, Felip E, Chia V, Glaser S, Pultar P, Zhao S, Peng B, Akimov M, Tan DSW. Phase Ib/II study of capmatinib (INC280) plus gefitinib after failure of epidermal growth factor receptor (EGFR) inhibitor therapy in patients with EGFR-mutated, MET factor-dysregulated non-small-cell lung cancer. J Clin Oncol 2018; 36(31): 3101–3109
CrossRef Google scholar
[160]
Scaranti M, Cojocaru E, Banerjee S, Banerji U. Exploiting the folate receptor α in oncology. Nat Rev Clin Oncol 2020; 17(6): 349–359
CrossRef Google scholar
[161]
Cheung A, Bax HJ, Josephs DH, Ilieva KM, Pellizzari G, Opzoomer J, Bloomfield J, Fittall M, Grigoriadis A, Figini M, Canevari S, Spicer JF, Tutt AN, Karagiannis SN. Targeting folate receptor alpha for cancer treatment. Oncotarget 2016; 7(32): 52553–52574
CrossRef Google scholar
[162]
Ab O, Whiteman KR, Bartle LM, Sun X, Singh R, Tavares D, LaBelle A, Payne G, Lutz RJ, Pinkas J, Goldmacher VS, Chittenden T, Lambert JM. IMGN853, a folate receptor-α (FRα)-targeting antibody-drug conjugate, exhibits potent targeted antitumor activity against FRα-expressing tumors. Mol Cancer Ther 2015; 14(7): 1605–1613
CrossRef Google scholar
[163]
Romero D. Mirvetuximab soravtansine has activity in platinum-sensitive epithelial ovarian cancer. Nat Rev Clin Oncol 2024; 21(6): 402
CrossRef Google scholar
[164]
Matulonis UA, Lorusso D, Oaknin A, Pignata S, Dean A, Denys H, Colombo N, Van Gorp T, Konner JA, Marin MR, Harter P, Murphy CG, Wang J, Noble E, Esteves B, Method M, Coleman RL. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: results from the SORAYA study. J Clin Oncol 2023; 41(13): 2436–2445
CrossRef Google scholar
[165]
Moore KN, Gorp TV, Wang J, Esteves B, Zweidler-McKay PA. MIRASOL (GOG 3045/ENGOT OV-55): a randomized, open-label, phase III study of mirvetuximab soravtansine versus investigator’s choice of chemotherapy in advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate-alpha (FRα) expression. J Clin Oncol 2020; 38(15 suppl): TPS6103
CrossRef Google scholar
[166]
Gong J, Hu X, Zhang J, Du Y, Huang R, Teng Y, Tan W, Shen L. Phase Ia study of CBP-1008, a bi-specific ligand drug conjugate targeting FRα and TRPV6, in patients with advanced solid tumors. J Clin Oncol 2021; 39(15 suppl): 3077
CrossRef Google scholar
[167]
Esapa B, Jiang J, Cheung A, Chenoweth A, Thurston DE, Karagiannis SN. Target antigen attributes and their contributions to clinically approved antibody-drug conjugates (ADCs) in haematopoietic and solid cancers. Cancers (Basel) 2023; 15(6): 1845
CrossRef Google scholar
[168]
Joubert N, Beck A, Dumontet C, Denevault-Sabourin C. Antibody-drug conjugates: the last decade. Pharmaceuticals (Basel) 2020; 13(9): 245
CrossRef Google scholar
[169]
Sun Y, Yu X, Wang X, Yuan K, Wang G, Hu L, Zhang G, Pei W, Wang L, Sun C, Yang P. Bispecific antibodies in cancer therapy: target selection and regulatory requirements. Acta Pharm Sin B 2023; 13(9): 3583–3597
CrossRef Google scholar
[170]
Jiang T, Shi T, Zhang H, Hu J, Song Y, Wei J, Ren S, Zhou C. Tumor neoantigens: from basic research to clinical applications. J Hematol Oncol 2019; 12(1): 93
CrossRef Google scholar
[171]
Gupta RG, Li F, Roszik J, Lizée G. Exploiting tumor neoantigens to target cancer evolution: current challenges and promising therapeutic approaches. Cancer Discov 2021; 11(5): 1024–1039
CrossRef Google scholar
[172]
Yarchoan M, Johnson BA 3rd, Lutz ER, Laheru DA, Jaffee EM. Targeting neoantigens to augment antitumour immunity. Nat Rev Cancer 2017; 17(4): 209–222
CrossRef Google scholar
[173]
Zhang Z, Rohweder PJ, Ongpipattanakul C, Basu K, Bohn MF, Dugan EJ, Steri V, Hann B, Shokat KM, Craik CS. A covalent inhibitor of K-Ras(G12C) induces MHC class I presentation of haptenated peptide neoepitopes targetable by immunotherapy. Cancer Cell 2022; 40(9): 1060–1069. e7
CrossRef Google scholar
[174]
Williams DB, Vassilakos A, Suh WK. Peptide presentation by MHC class I molecules. Trends Cell Biol 1996; 6(7): 267–273
CrossRef Google scholar
[175]
Hattori T, Maso L, Araki KY, Koide A, Hayman J, Akkapeddi P, Bang I, Neel BG, Koide S. Creating MHC-restricted neoantigens with covalent inhibitors that can be targeted by immune therapy. Cancer Discov 2023; 13(1): 132–145
CrossRef Google scholar
[176]
Douglass J, Hsiue EH, Mog BJ, Hwang MS, DiNapoli SR, Pearlman AH, Miller MS, Wright KM, Azurmendi PA, Wang Q, Paul S, Schaefer A, Skora AD, Molin MD, Konig MF, Liu Q, Watson E, Li Y, Murphy MB, Pardoll DM, Bettegowda C, Papadopoulos N, Gabelli SB, Kinzler KW, Vogelstein B, Zhou S. Bispecific antibodies targeting mutant RAS neoantigens. Sci Immunol 2021; 6(57): eabd5515
CrossRef Google scholar
[177]
Hsiue EHC, Wright KM, Douglass J, Hwang MS, Mog BJ, Pearlman AH, Paul S, DiNapoli SR, Konig MF, Wang Q, Schaefer A, Miller MS, Skora AD, Azurmendi PA, Murphy MB, Liu Q, Watson E, Li Y, Pardoll DM, Bettegowda C, Papadopoulos N, Kinzler KW, Vogelstein B, Gabelli SB, Zhou S. Targeting a neoantigen derived from a common TP53 mutation. Science 2021; 371(6533): eabc8697
CrossRef Google scholar
[178]
Shen Y, Wei X, Jin S, Wu Y, Zhao W, Xu Y, Pan L, Zhou Z, Chen S. TCR-mimic antibody-drug conjugates targeting intracellular tumor-specific mutant antigen KRAS G12V mutation. Asian J Pharm Sci 2020; 15(6): 777–785
CrossRef Google scholar
[179]
Marshall DJ, Harried SS, Murphy JL, Hall CA, Shekhani MS, Pain C, Lyons CA, Chillemi A, Malavasi F, Pearce HL, Thorson JS, Prudent JR. Extracellular antibody drug conjugates exploiting the proximity of two proteins. Mol Ther 2016; 24(10): 1760–1770
CrossRef Google scholar
[180]
Polson AG, Calemine-Fenaux J, Chan P, Chang W, Christensen E, Clark S, de Sauvage FJ, Eaton D, Elkins K, Elliott JM, Frantz G, Fuji RN, Gray A, Harden K, Ingle GS, Kljavin NM, Koeppen H, Nelson C, Prabhu S, Raab H, Ross S, Slaga DS, Stephan JP, Scales SJ, Spencer SD, Vandlen R, Wranik B, Yu SF, Zheng B, Ebens A. Antibody-drug conjugates for the treatment of non-Hodgkin’s lymphoma: target and linker-drug selection. Cancer Res 2009; 69(6): 2358–2364
CrossRef Google scholar
[181]
Govindan SV, Cardillo TM, Moon SJ, Hansen HJ, Goldenberg DM. CEACAM5-targeted therapy of human colonic and pancreatic cancer xenografts with potent labetuzumab-SN-38 immunoconjugates. Clin Cancer Res 2009; 15(19): 6052–6061
CrossRef Google scholar
[182]
Javaid F, Pilotti C, Camilli C, Kallenberg D, Bahou C, Blackburn J, Baker JR, Greenwood J, Moss SE, Chudasama V. Leucine-rich alpha-2-glycoprotein 1 (LRG1) as a novel ADC target. RSC Chem Biol 2021; 2(4): 1206–1220
CrossRef Google scholar
[183]
Sau S, Petrovici A, Alsaab HO, Bhise K, Iyer AK. PDL-1 antibody drug conjugate for selective chemo-guided immune modulation of cancer. Cancers (Basel) 2019; 11(2): 232
CrossRef Google scholar
[184]
Giansanti F, Capone E, Ponziani S, Piccolo E, Gentile R, Lamolinara A, Di Campli A, Sallese M, Iacobelli V, Cimini A, De Laurenzi V, Lattanzio R, Piantelli M, Ippoliti R, Sala G, Iacobelli S. Secreted Gal-3BP is a novel promising target for non-internalizing antibody-drug conjugates. J Control Release 2019; 294: 176–184
CrossRef Google scholar
[185]
Awasthi N, Mikels-Vigdal AJ, Stefanutti E, Schwarz MA, Monahan S, Smith V, Schwarz RE. Therapeutic efficacy of anti-MMP9 antibody in combination with nab-paclitaxel-based chemotherapy in pre-clinical models of pancreatic cancer. J Cell Mol Med 2019; 23(6): 3878–3887
CrossRef Google scholar
[186]
Yap ML, McFadyen JD, Wang X, Ziegler M, Chen YC, Willcox A, Nowell CJ, Scott AM, Sloan EK, Hogarth PM, Pietersz GA, Peter K. Activated platelets in the tumor microenvironment for targeting of antibody-drug conjugates to tumors and metastases. Theranostics 2019; 9(4): 1154–1169
CrossRef Google scholar
[187]
Bernardes GJ, Casi G, Trüssel S, Hartmann I, Schwager K, Scheuermann J, Neri D. A traceless vascular-targeting antibody-drug conjugate for cancer therapy. Angew Chem Int Ed Engl 2012; 51(4): 941–944
CrossRef Google scholar
[188]
Polu KR, Lowman HB. Probody therapeutics for targeting antibodies to diseased tissue. Expert Opin Biol Ther 2014; 14(8): 1049–1053
CrossRef Google scholar
[189]
Desnoyers LR, Vasiljeva O, Richardson JH, Yang A, Menendez EE, Liang TW, Wong C, Bessette PH, Kamath K, Moore SJ, Sagert JG, Hostetter DR, Han F, Gee J, Flandez J, Markham K, Nguyen M, Krimm M, Wong KR, Liu S, Daugherty PS, West JW, Lowman HB. Tumor-specific activation of an EGFR-targeting probody enhances therapeutic index. Sci Transl Med 2013; 5(207): 207ra144
CrossRef Google scholar
[190]
Autio KA, Boni V, Humphrey RW, Naing A. Probody therapeutics: an emerging class of therapies designed to enhance on-target effects with reduced off-tumor toxicity for use in immuno-oncology. Clin Cancer Res 2020; 26(5): 984–989
CrossRef Google scholar
[191]
Chomet M, Schreurs M, Nguyen M, Howng B, Villanueva R, Krimm M, Vasiljeva O, van Dongen GAMS, Vugts DJ. The tumor targeting performance of anti-CD166 probody drug conjugate CX-2009 and its parental derivatives as monitored by 89Zr-immuno-PET in xenograft bearing mice. Theranostics 2020; 10(13): 5815–5828
CrossRef Google scholar
[192]
Singh S, Serwer L, DuPage A, Elkins K, Chauhan N, Ravn M, Buchanan F, Wang L, Krimm M, Wong K, Sagert J, Tipton K, Moore SJ, Huang Y, Jang A, Ureno E, Miller A, Patrick S, Duvur S, Liu S, Vasiljeva O, Li Y, Henriques T, Badagnani I, Jeffries S, Schleyer S, Leanna R, Krebber C, Viswanathan S, Desnoyers L, Terrett J, Belvin M, Morgan-Lappe S, Kavanaugh WM, Richardson J. Nonclinical efficacy and safety of CX-2029, an anti-CD71 probody-drug conjugate. Mol Cancer Ther 2022; 21(8): 1326–1336
CrossRef Google scholar
[193]
Johnson M, El-Khoueiry A, Hafez N, Lakhani N, Mamdani H, Rodon J, Sanborn RE, Garcia-Corbacho J, Boni V, Stroh M, Hannah AL, Wang S, Castro H, Spira A. Phase I, first-in-human study of the probody therapeutic CX-2029 in adults with advanced solid tumor malignancies. Clin Cancer Res 2021; 27(16): 4521–4530
CrossRef Google scholar
[194]
Li Y, Liu J, Chen W, Wang W, Yang F, Liu X, Sheng Y, Du K, He M, Lyu X, Li H, Zhao L, Wei Z, Wang F, Zheng S, Sui J. A pH-dependent anti-CD47 antibody that selectively targets solid tumors and improves therapeutic efficacy and safety. J Hematol Oncol 2023; 16(1): 2
CrossRef Google scholar
[195]
Kamata-Sakurai M, Narita Y, Hori Y, Nemoto T, Uchikawa R, Honda M, Hironiwa N, Taniguchi K, Shida-Kawazoe M, Metsugi S, Miyazaki T, Wada NA, Ohte Y, Shimizu S, Mikami H, Tachibana T, Ono N, Adachi K, Sakiyama T, Matsushita T, Kadono S, Komatsu SI, Sakamoto A, Horikawa S, Hirako A, Hamada K, Naoi S, Savory N, Satoh Y, Sato M, Noguchi Y, Shinozuka J, Kuroi H, Ito A, Wakabayashi T, Kamimura M, Isomura F, Tomii Y, Sawada N, Kato A, Ueda O, Nakanishi Y, Endo M, Jishage KI, Kawabe Y, Kitazawa T, Igawa T. Antibody to CD137 activated by extracellular adenosine triphosphate is tumor selective and broadly effective in vivo without systemic immune activation. Cancer Discov 2021; 11(1): 158–175
CrossRef Google scholar
[196]
Sulea T, Rohani N, Baardsnes J, Corbeil CR, Deprez C, Cepero-Donates Y, Robert A, Schrag JD, Parat M, Duchesne M, Jaramillo ML, Purisima EO, Zwaagstra JC. Structure-based engineering of pH-dependent antibody binding for selective targeting of solid-tumor microenvironment. MAbs 2020; 12(1): 1682866
CrossRef Google scholar
[197]
Han S, Lim KS, Blackburn BJ, Yun J, Putnam CW, Bull DA, Won YW. The potential of topoisomerase inhibitor-based antibody-drug conjugates. Pharmaceutics 2022; 14(8): 1707
CrossRef Google scholar
[198]
Doronina SO, Bovee TD, Meyer DW, Miyamoto JB, Anderson ME, Morris-Tilden CA, Senter PD. Novel peptide linkers for highly potent antibody-auristatin conjugate. Bioconjug Chem 2008; 19(10): 1960–1963
CrossRef Google scholar
[199]
Lyon RP, Bovee TD, Doronina SO, Burke PJ, Hunter JH, Neff-LaFord HD, Jonas M, Anderson ME, Setter JR, Senter PD. Reducing hydrophobicity of homogeneous antibody-drug conjugates improves pharmacokinetics and therapeutic index. Nat Biotechnol 2015; 33(7): 733–735
CrossRef Google scholar
[200]
Iwata TN, Ishii C, Ishida S, Ogitani Y, Wada T, Agatsuma T. A HER2-targeting antibody-drug conjugate, trastuzumab deruxtecan (DS-8201a), enhances antitumor immunity in a mouse model. Mol Cancer Ther 2018; 17(7): 1494–1503
CrossRef Google scholar
[201]
Ogitani Y, Aida T, Hagihara K, Yamaguchi J, Ishii C, Harada N, Soma M, Okamoto H, Oitate M, Arakawa S, Hirai T, Atsumi R, Nakada T, Hayakawa I, Abe Y, Agatsuma T. DS-8201a, a novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1. Clin Cancer Res 2016; 22(20): 5097–5108
CrossRef Google scholar
[202]
Matsuda Y, Mendelsohn BA. An overview of process development for antibody-drug conjugates produced by chemical conjugation technology. Expert Opin Biol Ther 2021; 21(7): 963–975
CrossRef Google scholar
[203]
Sheyi R, de la Torre BG, Albericio F. Linkers: an assurance for controlled delivery of antibody-drug conjugate. Pharmaceutics 2022; 14(2): 396
CrossRef Google scholar
[204]
Xu Y, Jiang G, Tran C, Li X, Heibeck TH, Masikat MR, Cai Q, Steiner AR, Sato AK, Hallam TJ, Yin G. RP-HPLC DAR characterization of site-specific antibody drug conjugates produced in a cell-free expression system. Org Process Res Dev 2016; 20(6): 1034–1043
CrossRef Google scholar
[205]
Barnscher S, Babcook J, Rich J, Winters G, Garnett G, Hernandez A, Fung V, Yin K, Hamblett K, Davies R. Abstract 61: Zymelink drug conjugate platform: redefining the therapeutic window for ADCs. Cancer Res 2017; 77(13 Supplement): 61
CrossRef Google scholar
[206]
Mazor Y, Sachsenmeier KF, Yang C, Hansen A, Filderman J, Mulgrew K, Wu H, Dall’Acqua WF. Enhanced tumor-targeting selectivity by modulating bispecific antibody binding affinity and format valence. Sci Rep 2017; 7(1): 40098
CrossRef Google scholar
[207]
Sellmann C, Doerner A, Knuehl C, Rasche N, Sood V, Krah S, Rhiel L, Messemer A, Wesolowski J, Schuette M, Becker S, Toleikis L, Kolmar H, Hock B. Balancing selectivity and efficacy of bispecific epidermal growth factor receptor (EGFR) × c-MET antibodies and antibody-drug conjugates. J Biol Chem 2016; 291(48): 25106–25119
CrossRef Google scholar
[208]
Andreev J, Thambi N, Perez Bay AE, Delfino F, Martin J, Kelly MP, Kirshner JR, Rafique A, Kunz A, Nittoli T, MacDonald D, Daly C, Olson W, Thurston G. Bispecific antibodies and antibody-drug conjugates (ADCs) bridging HER2 and prolactin receptor improve efficacy of HER2 ADCs. Mol Cancer Ther 2017; 16(4): 681–693
CrossRef Google scholar
[209]
Hu S, Fu W, Xu W, Yang Y, Cruz M, Berezov SD, Jorissen D, Takeda H, Zhu W. Four-in-one antibodies have superior cancer inhibitory activity against EGFR, HER2, HER3, and VEGF through disruption of HER/MET crosstalk. Cancer Res 2015; 75(1): 159–170
CrossRef Google scholar
[210]
Nessler I, Khera E, Vance S, Kopp A, Qiu Q, Keating TA, Abu-Yousif AO, Sandal T, Legg J, Thompson L, Goodwin N, Thurber GM. Increased tumor penetration of single-domain antibody-drug conjugates improves in vivo efficacy in prostate cancer models. Cancer Res 2020; 80(6): 1268–1278
CrossRef Google scholar
[211]
Deonarain MP, Xue Q. Tackling solid tumour therapy with small-format drug conjugates. Antib Ther 2020; 3(4): 237–245
CrossRef Google scholar
[212]
Kholodenko RV, Kalinovsky DV, Doronin II, Ponomarev ED, Kholodenko IV. Antibody fragments as potential biopharmaceuticals for cancer therapy: success and limitations. Curr Med Chem 2019; 26(3): 396–426
CrossRef Google scholar
[213]
Deonarain MP, Yahioglu G, Stamati I, Pomowski A, Clarke J, Edwards BM, Diez-Posada S, Stewart AC. Small-format drug conjugates: a viable alternative to ADCs for solid tumours. Antibodies (Basel) 2018; 7(2): 16
CrossRef Google scholar
[214]
Wu Y, Li Q, Kong Y, Wang Z, Lei C, Li J, Ding L, Wang C, Cheng Y, Wei Y, Song Y, Yang Z, Tu C, Ding Y, Ying T. A highly stable human single-domain antibody-drug conjugate exhibits superior penetration and treatment of solid tumors. Mol Ther 2022; 30(8): 2785–2799
CrossRef Google scholar
[215]
Huang H, Wu T, Shi H, Wu Y, Yang H, Zhong K, Wang Y, Liu Y. Modular design of nanobody-drug conjugates for targeted-delivery of platinum anticancer drugs with an MRI contrast agent. Chem Commun (Camb) 2019; 55(35): 5175–5178
CrossRef Google scholar
[216]
Vallera DA, Chen H, Sicheneder AR, Panoskaltsis-Mortari A, Taras EP. Genetic alteration of a bispecific ligand-directed toxin targeting human CD19 and CD22 receptors resulting in improved efficacy against systemic B cell malignancy. Leuk Res 2009; 33(9): 1233–1242
CrossRef Google scholar
[217]
Waldron NN, Barsky SH, Dougherty PR, Vallera DA. A bispecific EpCAM/CD133-targeted toxin is effective against carcinoma. Target Oncol 2014; 9(3): 239–249
CrossRef Google scholar
[218]
Porębska N, Ciura K, Chorążewska A, Zakrzewska M, Otlewski J, Opaliński Ł. Multivalent protein-drug conjugates—an emerging strategy for the upgraded precision and efficiency of drug delivery to cancer cells. Biotechnol Adv 2023; 67: 108213
CrossRef Google scholar
[219]
Zhou L, Yang F, Bai Z, Zhou X, Zhang Z, Li Z, Gong J, Yu J, Pan L, Cao C, Chou JJ. Self-assembled L-DNA linkers for rapid construction of multi-specific antibody-drug conjugates library. Angew Chem Int Ed Engl 2023; 62(27): e202302805
CrossRef Google scholar
[220]
Kim YE, Kim YN, Kim JA, Kim HM, Jung Y. Green fluorescent protein nanopolygons as monodisperse supramolecular assemblies of functional proteins with defined valency. Nat Commun 2015; 6(1): 7134
CrossRef Google scholar
[221]
Porębska N, Knapik A, Poźniak M, Krzyścik MA, Zakrzewska M, Otlewski J, Opaliński Ł. Intrinsically fluorescent oligomeric cytotoxic conjugates toxic for FGFR1-overproducing cancers. Biomacromolecules 2021; 22(12): 5349–5362
CrossRef Google scholar
[222]
Dundas CM, Demonte D, Park S. Streptavidin-biotin technology: improvements and innovations in chemical and biological applications. Appl Microbiol Biotechnol 2013; 97(21): 9343–9353
CrossRef Google scholar
[223]
Le Q, Nguyen V, Park S. Recent advances in the engineering and application of streptavidin-like molecules. Appl Microbiol Biotechnol 2019; 103(18): 7355–7365
CrossRef Google scholar
[224]
Tremante E, Sibilio L, Centola F, Knutti N, Holzapfel G, Manni I, Allegretti M, Lombardi P, Salvo G, Cecchetelli L, Friedrich K, Bertram J, Giacomini P. TOOLBOX: Strep-Tagged nano-assemblies of antibody-drug-conjugates (ADC) for modular and conditional cancer drugging. Oncol Rep 2021; 45(5): 77
CrossRef Google scholar
[225]
Lázaro-Gorines R, Ruiz-de-la-Herrán J, Navarro R, Sanz L, Álvarez-Vallina L, Martínez-Del-Pozo A, Gavilanes JG, Lacadena J. A novel carcinoembryonic antigen (CEA)-targeted trimeric immunotoxin shows significantly enhanced antitumor activity in human colorectal cancer xenografts. Sci Rep 2019; 9(1): 11680
CrossRef Google scholar
[226]
Yamaguchi A, Anami Y, Ha SYY, Roeder TJ, Xiong W, Lee J, Ueno NT, Zhang N, An Z, Tsuchikama K. Chemical generation of small molecule-based bispecific antibody-drug conjugates for broadening the target scope. Bioorg Med Chem 2021; 32: 116013
CrossRef Google scholar

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 32070940 and 81991491), China Postdoctoral Science Foundation (No. 2021M700115), Postdoctoral Innovation Talents Support Program (No. BX20220189), CAMS Innovation Fund for Medical Sciences (No. 2019RU022), and Fundamental Research Funds for the Central Universities (No. 20720220006).

Compliance with ethics guidelines

Conflicts of interest Hongye Zeng, Wenjing Ning, Xue Liu, Wenxin Luo, and Ningshao Xia declare no potential conflicts of interest.
This manuscript is a review article and does not involve a research protocol requiring approval by an institutional review board or ethics committee.

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