Emerging immunological strategies: recent advances and future directions
Hongyun Zhao, Fan Luo, Jinhui Xue, Su Li, Rui-Hua Xu
Emerging immunological strategies: recent advances and future directions
Immunotherapy plays a compelling role in cancer treatment and has already made remarkable progress. However, many patients receiving immune checkpoint inhibitors fail to achieve clinical benefits, and the response rates vary among tumor types. New approaches that promote anti-tumor immunity have recently been developed, such as small molecules, bispecific antibodies, chimeric antigen receptor T cell products, and cancer vaccines. Small molecule drugs include agonists and inhibitors that can reach the intracellular or extracellular targets of immune cells participating in innate or adaptive immune pathways. Bispecific antibodies, which bind two different antigens or one antigen with two different epitopes, are of great interest. Chimeric antigen receptor T cell products and cancer vaccines have also been investigated. This review explores the recent progress and challenges of different forms of immunotherapy agents and provides an insight into future immunotherapeutic strategies.
cancer immunotherapy / bispecific antibodies / small molecules / chimeric antigen receptor T therapy / cancer vaccines
[1] |
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366(26): 2443–2454
CrossRef
Pubmed
Google scholar
|
[2] |
Skoulidis F, Goldberg ME, Greenawalt DM, Hellmann MD, Awad MM, Gainor JF, Schrock AB, Hartmaier RJ, Trabucco SE, Gay L, Ali SM, Elvin JA, Singal G, Ross JS, Fabrizio D, Szabo PM, Chang H, Sasson A, Srinivasan S, Kirov S, Szustakowski J, Vitazka P, Edwards R, Bufill JA, Sharma N, Ou SI, Peled N, Spigel DR, Rizvi H, Aguilar EJ, Carter BW, Erasmus J, Halpenny DF, Plodkowski AJ, Long NM, Nishino M, Denning WL, Galan-Cobo A, Hamdi H, Hirz T, Tong P, Wang J, Rodriguez-Canales J, Villalobos PA, Parra ER, Kalhor N, Sholl LM, Sauter JL, Jungbluth AA, Mino-Kenudson M, Azimi R, Elamin YY, Zhang J, Leonardi GC, Jiang F, Wong KK, Lee JJ, Papadimitrakopoulou VA, Wistuba II, Miller VA, Frampton GM, Wolchok JD, Shaw AT, Jänne PA, Stephens PJ, Rudin CM, Geese WJ, Albacker LA, Heymach JV. STK11/LKB1 mutations and PD-1 inhibitor resistance in KRAS-mutant lung adenocarcinoma. Cancer Discov 2018; 8(7): 822–835
CrossRef
Pubmed
Google scholar
|
[3] |
Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med 2018; 378(2): 158–168
CrossRef
Pubmed
Google scholar
|
[4] |
van der Zanden SY, Luimstra JJ, Neefjes J, Borst J, Ovaa H. Opportunities for small molecules in cancer immunotherapy. Trends Immunol 2020; 41(6): 493–511
CrossRef
Pubmed
Google scholar
|
[5] |
Skalniak L, Zak KM, Guzik K, Magiera K, Musielak B, Pachota M, Szelazek B, Kocik J, Grudnik P, Tomala M, Krzanik S, Pyrc K, Dömling A, Dubin G, Holak TA. Small-molecule inhibitors of PD-1/PD-L1 immune checkpoint alleviate the PD-L1-induced exhaustion of T-cells. Oncotarget 2017; 8(42): 72167–72181
CrossRef
Pubmed
Google scholar
|
[6] |
Ganesan A, Ahmed M, Okoye I, Arutyunova E, Babu D, Turnbull WL, Kundu JK, Shields J, Agopsowicz KC, Xu L, Tabana Y, Srivastava N, Zhang G, Moon TC, Belovodskiy A, Hena M, Kandadai AS, Hosseini SN, Hitt M, Walker J, Smylie M, West FG, Siraki AG, Lemieux MJ, Elahi S, Nieman JA, Tyrrell DL, Houghton M, Barakat K. Comprehensive in vitro characterization of PD-L1 small molecule inhibitors. Sci Rep 2019; 9(1): 12392
CrossRef
Pubmed
Google scholar
|
[7] |
Chen FF, Li Z, Ma D, Yu Q. Small-molecule PD-L1 inhibitor BMS1166 abrogates the function of PD-L1 by blocking its ER export. OncoImmunology 2020; 9(1): 1831153
CrossRef
Pubmed
Google scholar
|
[8] |
Guzik K, Zak KM, Grudnik P, Magiera K, Musielak B, Törner R, Skalniak L, Dömling A, Dubin G, Holak TA. Small-molecule inhibitors of the programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) interaction via transiently induced protein states and dimerization of PD-L1. J Med Chem 2017; 60(13): 5857–5867
CrossRef
Pubmed
Google scholar
|
[9] |
Zak KM, Grudnik P, Guzik K, Zieba BJ, Musielak B, Dömling A, Dubin G, Holak TA. Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1). Oncotarget 2016; 7(21): 30323–30335
CrossRef
Pubmed
Google scholar
|
[10] |
Sasikumar P, Sudarshan N, Ramachandra R, Gowda N, Samiulla D, Bilugudi P, Adurthi S, Mani J, Nair R, Ramachandra M. Pre-clinical efficacy in multiple syngeneic models with oral immune checkpoint antagonists targeting PD-L1 and TIM-3. Eur J Cancer 2016; 1(69): S98
CrossRef
Google scholar
|
[11] |
Powderly J, Patel M, Lee J, Brody J, Meric-Bernstam F, Hamilton E, Aix SP, Garcia-Corbacho J, Bang Y, Ahn M. CA-170, a first in class oral small molecule dual inhibitor of immune checkpoints PD-L1 and VISTA, demonstrates tumor growth inhibition in pre-clinical models and promotes T cell activation in Phase 1 study. Ann Oncol 2017; 28: v405–v406
CrossRef
Google scholar
|
[12] |
Radhakrishnan V, Banavali S, Gupta S, Kumar A, Deshmukh C, Nag S, Beniwal S, Gopichand M, Naik R, Lakshmaiah K, Mandavia D, Ramchandra M, Prabhash K. Excellent CBR and prolonged PFS in non-squamous NSCLC with oral CA-170, an inhibitor of VISTA and PD-L1. Ann Oncol 2019; 30: v494
CrossRef
Google scholar
|
[13] |
Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 2010; 11(5): 373–384
CrossRef
Pubmed
Google scholar
|
[14] |
Work Group; Invited Reviewers, Kim JYS, Kozlow JH, Mittal B, Moyer J, Olencki T, Rodgers P. Guidelines of care for the management of basal cell carcinoma. J Am Acad Dermatol 2018; 78(3): 540–559
CrossRef
Pubmed
Google scholar
|
[15] |
Donin NM, Chamie K, Lenis AT, Pantuck AJ, Reddy M, Kivlin D, Holldack J, Pozzi R, Hakim G, Karsh LI, Lamm DL, Belkoff LH, Belldegrun AS, Holden S, Shore N. A phase 2 study of TMX-101, intravesical imiquimod, for the treatment of carcinoma in situ bladder cancer. Urol Oncol 2017; 35(2): 39.e1–39.e7
CrossRef
Pubmed
Google scholar
|
[16] |
Dietsch GN, Lu H, Yang Y, Morishima C, Chow LQ, Disis ML, Hershberg RM. Coordinated activation of Toll-like receptor 8 (TLR8) and NLRP3 by the TLR8 agonist, VTX-2337, ignites tumoricidal natural killer cell activity. PLoS One 2016; 11(2): e0148764
CrossRef
Pubmed
Google scholar
|
[17] |
Rodell CB, Arlauckas SP, Cuccarese MF, Garris CS, Li R, Ahmed MS, Kohler RH, Pittet MJ, Weissleder R. TLR7/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapy. Nat Biomed Eng 2018; 2(8): 578–588
CrossRef
Pubmed
Google scholar
|
[18] |
Woo SR, Fuertes MB, Corrales L, Spranger S, Furdyna MJ, Leung MY, Duggan R, Wang Y, Barber GN, Fitzgerald KA, Alegre ML, Gajewski TF. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity 2014; 41(5): 830–842
CrossRef
Pubmed
Google scholar
|
[19] |
Corrales L, Glickman LH, McWhirter SM, Kanne DB, Sivick KE, Katibah GE, Woo SR, Lemmens E, Banda T, Leong JJ, Metchette K, Dubensky TW Jr, Gajewski TF. Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity. Cell Rep 2015; 11(7): 1018–1030
CrossRef
Pubmed
Google scholar
|
[20] |
Sivick KE, Desbien AL, Glickman LH, Reiner GL, Corrales L, Surh NH, Hudson TE, Vu UT, Francica BJ, Banda T, Katibah GE, Kanne DB, Leong JJ, Metchette K, Bruml JR, Ndubaku CO, McKenna JM, Feng Y, Zheng L, Bender SL, Cho CY, Leong ML, van Elsas A, Dubensky TW Jr, McWhirter SM. Magnitude of therapeutic STING activation determines CD8+ T cell-mediated anti-tumor immunity. Cell Rep 2018; 25(11): 3074–3085.e5
CrossRef
Pubmed
Google scholar
|
[21] |
Meric-Bernstam F, Sandhu S K, Hamid O, Spreafico A, Kasper S, Dummer R, Shimizu T, Steeghs N, Lewis N, Talluto C. Phase Ib study of MIW815 (ADU-S100) in combination with spartalizumab (PDR001) in patients (pts) with advanced/metastatic solid tumors or lymphomas. J Clin Oncol 2019; 37 (15_suppl): 2507
CrossRef
Google scholar
|
[22] |
Tye H, Kennedy CL, Najdovska M, McLeod L, McCormack W, Hughes N, Dev A, Sievert W, Ooi CH, Ishikawa TO, Oshima H, Bhathal PS, Parker AE, Oshima M, Tan P, Jenkins BJ. STAT3-driven upregulation of TLR2 promotes gastric tumorigenesis independent of tumor inflammation. Cancer Cell 2012; 22(4): 466–478
CrossRef
Pubmed
Google scholar
|
[23] |
Ochi A, Graffeo CS, Zambirinis CP, Rehman A, Hackman M, Fallon N, Barilla RM, Henning JR, Jamal M, Rao R, Greco S, Deutsch M, Medina-Zea MV, Bin Saeed U, Ego-Osuala MO, Hajdu C, Miller G. Toll-like receptor 7 regulates pancreatic carcinogenesis in mice and humans. J Clin Invest 2012; 122(11): 4118–4129
CrossRef
Pubmed
Google scholar
|
[24] |
Li X, Wenes M, Romero P, Huang SC, Fendt SM, Ho PC. Navigating metabolic pathways to enhance antitumour immunity and immunotherapy. Nat Rev Clin Oncol 2019; 16(7): 425–441
CrossRef
Pubmed
Google scholar
|
[25] |
Liu X, Shin N, Koblish HK, Yang G, Wang Q, Wang K, Leffet L, Hansbury MJ, Thomas B, Rupar M, Waeltz P, Bowman KJ, Polam P, Sparks RB, Yue EW, Li Y, Wynn R, Fridman JS, Burn TC, Combs AP, Newton RC, Scherle PA. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood 2010; 115(17): 3520–3530
CrossRef
Pubmed
Google scholar
|
[26] |
Luke J, Tabernero J, Joshua A, Desai J, Varga A, Moreno V, Gomez-Roca C, Markman B, Braud F, Patel S, Carlino M, Siu L, Curigliano G, Liu Z, Ishii Y, Wind-Rotolo M, Basciano P, Azrilevich A, Gelmon K. BMS-986205, an indoleamine 2, 3-dioxygenase 1 inhibitor (IDO1i), in combination with nivolumab (nivo): Updated safety across all tumor cohorts and efficacy in advanced bladder cancer (advBC). J Clin Oncol 2019; 37(7 suppl): 358
CrossRef
Google scholar
|
[27] |
Jung KH, LoRusso P, Burris H, Gordon M, Bang YJ, Hellmann MD, Cervantes A, Ochoa de Olza M, Marabelle A, Hodi FS, Ahn MJ, Emens LA, Barlesi F, Hamid O, Calvo E, McDermott D, Soliman H, Rhee I, Lin R, Pourmohamad T, Suchomel J, Tsuhako A, Morrissey K, Mahrus S, Morley R, Pirzkall A, Davis SL. Phase I study of the indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor navoximod (GDC-0919) administered with PD-L1 inhibitor (atezolizumab) in advanced solid tumors. Clin Cancer Res 2019; 25(11): 3220–3228
CrossRef
Pubmed
Google scholar
|
[28] |
Long GV, Dummer R, Hamid O, Gajewski TF, Caglevic C, Dalle S, Arance A, Carlino MS, Grob JJ, Kim TM, Demidov L, Robert C, Larkin J, Anderson JR, Maleski J, Jones M, Diede SJ, Mitchell TC. Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study. Lancet Oncol 2019; 20(8): 1083–1097
CrossRef
Pubmed
Google scholar
|
[29] |
Adams JL, Smothers J, Srinivasan R, Hoos A. Big opportunities for small molecules in immuno-oncology. Nat Rev Drug Discov 2015; 14(9): 603–622
CrossRef
Pubmed
Google scholar
|
[30] |
Steggerda SM, Bennett MK, Chen J, Emberley E, Huang T, Janes JR, Li W, MacKinnon AL, Makkouk A, Marguier G, Murray PJ, Neou S, Pan A, Parlati F, Rodriguez MLM, Van de Velde LA, Wang T, Works M, Zhang J, Zhang W, Gross MI. Inhibition of arginase by CB-1158 blocks myeloid cell-mediated immune suppression in the tumor microenvironment. J Immunother Cancer 2017; 5(1): 101
CrossRef
Pubmed
Google scholar
|
[31] |
Johnson M O, Wolf M, Madden M Z, Andrejeva G, Sugiura A, Contreras D C, Maseda D, Liberti M V, Paz K, Kishton R J, Johnson M E, de Cubas A, Wu P, Li G, Zhang Y, Newcomb D C, Wells A D, Restifo N P, Rathmell W K, Locasale J W, Davila M L, Blazar B R, Rathmell J C. Distinct regulation of Th17 and Th1 cell differentiation by glutaminase-dependent metabolism. Cell 2018; 175(7): 1780–1795.e1719
CrossRef
Google scholar
|
[32] |
Deaglio S, Dwyer KM, Gao W, Friedman D, Usheva A, Erat A, Chen JF, Enjyoji K, Linden J, Oukka M, Kuchroo VK, Strom TB, Robson SC. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med 2007; 204(6): 1257–1265
CrossRef
Pubmed
Google scholar
|
[33] |
Beavis PA, Milenkovski N, Henderson MA, John LB, Allard B, Loi S, Kershaw MH, Stagg J, Darcy PK. Adenosine Receptor 2A Blockade Increases the Efficacy of Anti-PD-1 through Enhanced Antitumor T-cell Responses. Cancer Immunol Res 2015; 3(5): 506–517
CrossRef
Pubmed
Google scholar
|
[34] |
Emens L, Powderly J, Fong L, Brody J, Forde P, Hellmann M, Hughes B, Kummar S, Loi S, Luke J. CPI-444, an oral adenosine A2a receptor (A2aR) antagonist, demonstrates clinical activity in patients with advanced solid tumors. Cancer Res 2017; 77(13 suppl): CT119
CrossRef
Google scholar
|
[35] |
Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 2006; 126(6): 1121–1133
CrossRef
Pubmed
Google scholar
|
[36] |
Hu X, Liu X, Moisan J, Wang Y, Lesch CA, Spooner C, Morgan RW, Zawidzka EM, Mertz D, Bousley D, Majchrzak K, Kryczek I, Taylor C, Van Huis C, Skalitzky D, Hurd A, Aicher TD, Toogood PL, Glick GD, Paulos CM, Zou W, Carter LL. Synthetic RORγ agonists regulate multiple pathways to enhance antitumor immunity. OncoImmunology 2016; 5(12): e1254854
CrossRef
Pubmed
Google scholar
|
[37] |
Herbertz S, Sawyer JS, Stauber AJ, Gueorguieva I, Driscoll KE, Estrem ST, Cleverly AL, Desaiah D, Guba SC, Benhadji KA, Slapak CA, Lahn MMdevelopment, therapy. Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway. Drug Des Devel Ther 2015; 9: 4479–4499PMID: 26309397
CrossRef
Google scholar
|
[38] |
Holmgaard RB, Schaer DA, Li Y, Castaneda SP, Murphy MY, Xu X, Inigo I, Dobkin J, Manro JR, Iversen PW, Surguladze D, Hall GE, Novosiadly RD, Benhadji KA, Plowman GD, Kalos M, Driscoll KE. Targeting the TGFβ pathway with galunisertib, a TGFβRI small molecule inhibitor, promotes anti-tumor immunity leading to durable, complete responses, as monotherapy and in combination with checkpoint blockade. J Immunother Cancer 2018; 6(1): 47
CrossRef
Pubmed
Google scholar
|
[39] |
Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, Hashimoto-Tane A, Azuma M, Saito T. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med 2012; 209(6): 1201–1217
CrossRef
Pubmed
Google scholar
|
[40] |
Zhao M, Guo W, Wu Y, Yang C, Zhong L, Deng G, Zhu Y, Liu W, Gu Y, Lu Y, Kong L, Meng X, Xu Q, Sun Y. SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade. Acta Pharm Sin B 2019; 9(2): 304–315
CrossRef
Pubmed
Google scholar
|
[41] |
Dammeijer F, Lievense LA, Kaijen-Lambers ME, van Nimwegen M, Bezemer K, Hegmans JP, van Hall T, Hendriks RW, Aerts JG. Depletion of tumor-associated macrophages with a CSF-1R kinase inhibitor enhances antitumor immunity and survival induced by DC immunotherapy. Cancer Immunol Res 2017; 5(7): 535–546
CrossRef
Pubmed
Google scholar
|
[42] |
Gumbleton M, Sudan R, Fernandes S, Engelman RW, Russo CM, Chisholm JD, Kerr WG. Dual enhancement of T and NK cell function by pulsatile inhibition of SHIP1 improves antitumor immunity and survival. Sci Signal 2017; 10(500): eaam5353
CrossRef
Pubmed
Google scholar
|
[43] |
Evans CA, Liu T, Lescarbeau A, Nair SJ, Grenier L, Pradeilles JA, Glenadel Q, Tibbitts T, Rowley AM, DiNitto JP, Brophy EE, O’Hearn EL, Ali JA, Winkler DG, Goldstein SI, O’Hearn P, Martin CM, Hoyt JG, Soglia JR, Cheung C, Pink MM, Proctor JL, Palombella VJ, Tremblay MR, Castro AC. Discovery of a selective phosphoinositide-3-kinase (PI3K)-γ inhibitor (IPI-549) as an immuno-oncology clinical candidate. ACS Med Chem Lett 2016; 7(9): 862–867
CrossRef
Pubmed
Google scholar
|
[44] |
Dwyer CJ, Arhontoulis DC, Rangel Rivera GO, Knochelmann HM, Smith AS, Wyatt MM, Rubinstein MP, Atkinson C, Thaxton JE, Neskey DM, Paulos CM. Ex vivo blockade of PI3K gamma or delta signaling enhances the antitumor potency of adoptively transferred CD8+ T cells. Eur J Immunol 2020; 50(9): 1386–1399
CrossRef
Pubmed
Google scholar
|
[45] |
Long M, Beckwith K, Do P, Mundy BL, Gordon A, Lehman AM, Maddocks KJ, Cheney C, Jones JA, Flynn JM, Andritsos LA, Awan F, Fraietta JA, June CH, Maus MV, Woyach JA, Caligiuri MA, Johnson AJ, Muthusamy N, Byrd JC. Ibrutinib treatment improves T cell number and function in CLL patients. J Clin Invest 2017; 127(8): 3052–3064
CrossRef
Pubmed
Google scholar
|
[46] |
Zlotnik A, Yoshie O. The chemokine superfamily revisited. Immunity 2012; 36(5): 705–716
CrossRef
Pubmed
Google scholar
|
[47] |
Sanford DE, Belt BA, Panni RZ, Mayer A, Deshpande AD, Carpenter D, Mitchem JB, Plambeck-Suess SM, Worley LA, Goetz BD, Wang-Gillam A, Eberlein TJ, Denardo DG, Goedegebuure SP, Linehan DC. Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: a role for targeting the CCL2/CCR2 axis. Clin Cancer Res 2013; 19(13): 3404–3415
CrossRef
Pubmed
Google scholar
|
[48] |
Chen Y, Ramjiawan RR, Reiberger T, Ng MR, Hato T, Huang Y, Ochiai H, Kitahara S, Unan EC, Reddy TP, Fan C, Huang P, Bardeesy N, Zhu AX, Jain RK, Duda DG. CXCR4 inhibition in tumor microenvironment facilitates anti-programmed death receptor-1 immunotherapy in sorafenib-treated hepatocellular carcinoma in mice. Hepatology 2015; 61(5): 1591–1602
CrossRef
Pubmed
Google scholar
|
[49] |
Uy GL, Rettig MP, Motabi IH, McFarland K, Trinkaus KM, Hladnik LM, Kulkarni S, Abboud CN, Cashen AF, Stockerl-Goldstein KE, Vij R, Westervelt P, DiPersio JF. A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia. Blood 2012; 119(17): 3917–3924
CrossRef
Pubmed
Google scholar
|
[50] |
Nisonoff A, Wissler FC, Lipman LN. Properties of the major component of a peptic digest of rabbit antibody. Science 1960; 132(3441): 1770–1771
CrossRef
Pubmed
Google scholar
|
[51] |
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
Pubmed
Google scholar
|
[52] |
Chelius D, Ruf P, Gruber P, Plöscher M, Liedtke R, Gansberger E, Hess J, Wasiliu M, Lindhofer H. Structural and functional characterization of the trifunctional antibody catumaxomab. MAbs 2010; 2(3): 309–319
CrossRef
Pubmed
Google scholar
|
[53] |
Klinger M, Brandl C, Zugmaier G, Hijazi Y, Bargou RC, Topp MS, Gökbuget N, Neumann S, Goebeler M, Viardot A, Stelljes M, Brüggemann M, Hoelzer D, Degenhard E, Nagorsen D, Baeuerle PA, Wolf A, Kufer P. Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell-engaging CD19/CD3-bispecific BiTE antibody blinatumomab. Blood 2012; 119(26): 6226–6233
CrossRef
Pubmed
Google scholar
|
[54] |
Kitazawa T, Esaki K, Tachibana T, Ishii S, Soeda T, Muto A, Kawabe Y, Igawa T, Tsunoda H, Nogami K, Shima M, Hattori K. Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX/IXa and X/Xa, emicizumab, depends on its ability to bridge the antigens. Thromb Haemost 2017; 117(7): 1348–1357
CrossRef
Pubmed
Google scholar
|
[55] |
Dickopf S, Georges GJ, Brinkmann U. Format and geometries matter: structure-based design defines the functionality of bispecific antibodies. Comput Struct Biotechnol J 2020; 18: 1221–1227
CrossRef
Pubmed
Google scholar
|
[56] |
Mazor Y, Hansen A, Yang C, Chowdhury PS, Wang J, Stephens G, Wu H, Dall’Acqua WF. Insights into the molecular basis of a bispecific antibody’s target selectivity. MAbs 2015; 7(3): 461–469
CrossRef
Pubmed
Google scholar
|
[57] |
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
Pubmed
Google scholar
|
[58] |
Lopez-Albaitero A, Xu H, Guo H, Wang L, Wu Z, Tran H, Chandarlapaty S, Scaltriti M, Janjigian Y, de Stanchina E, Cheung NK. Overcoming resistance to HER2-targeted therapy with a novel HER2/CD3 bispecific antibody. OncoImmunology 2017; 6(3): e1267891
CrossRef
Pubmed
Google scholar
|
[59] |
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
Pubmed
Google scholar
|
[60] |
Thakur A, Huang M, Lum LG. Bispecific antibody based therapeutics: strengths and challenges. Blood Rev 2018; 32(4): 339–347
CrossRef
Pubmed
Google scholar
|
[61] |
Zhang MY, Lu JJ, Wang L, Gao ZC, Hu H, Ung CO, Wang YT. Development of monoclonal antibodies in China: overview and prospects. BioMed Res Int 2015; 2015: 168935
CrossRef
Pubmed
Google scholar
|
[62] |
Staerz UD, Kanagawa O, Bevan MJ. Hybrid antibodies can target sites for attack by T cells. Nature 1985; 314(6012): 628–631
CrossRef
Pubmed
Google scholar
|
[63] |
Staerz UD, Bevan MJ. Hybrid hybridoma producing a bispecific monoclonal antibody that can focus effector T-cell activity. Proc Natl Acad Sci USA 1986; 83(5): 1453–1457
CrossRef
Pubmed
Google scholar
|
[64] |
Kontermann RE. Dual targeting strategies with bispecific antibodies. MAbs 2012; 4(2): 182–197
CrossRef
Pubmed
Google scholar
|
[65] |
Nie S, Wang Z, Moscoso-Castro M, D’Souza P, Lei C, Xu J, Gu J. Biology drives the discovery of bispecific antibodies as innovative therapeutics. Antib Ther 2020; 3(1): 18–62
CrossRef
Pubmed
Google scholar
|
[66] |
Grugan KD, Dorn K, Jarantow SW, Bushey BS, Pardinas JR, Laquerre S, Moores SL, Chiu ML. Fc-mediated activity of EGFR x c-Met bispecific antibody JNJ-61186372 enhanced killing of lung cancer cells. MAbs 2017; 9(1): 114–126
CrossRef
Pubmed
Google scholar
|
[67] |
Wang Q, Chung CY, Chough S, Betenbaugh MJ. Antibody glycoengineering strategies in mammalian cells. Biotechnol Bioeng 2018; 115(6): 1378–1393
CrossRef
Pubmed
Google scholar
|
[68] |
Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Discov Today 2015; 20(7): 838–847
CrossRef
Pubmed
Google scholar
|
[69] |
Gupta A, Kumar Y. Bispecific antibodies: a novel approach for targeting prominent biomarkers. Hum Vaccin Immunother 2020; 16(11): 2831–2839
CrossRef
Pubmed
Google scholar
|
[70] |
Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Discov Today 2015; 20(7): 838–847PMID: 25728220
CrossRef
Google scholar
|
[71] |
Xu T, Tau X, Wang X, Li Q, Minjie P, Zhang H, Han L, Zhang Q. Patent US 10808043 (B2); PCT/CN2016/070447. 2020
|
[72] |
Li F, Zhang B, Ye P, Zhao J, Huang S, Jin C. Patent US 9745382 (B1); PCT/CN2017/093816, 2017
|
[73] |
Liu J, Song N, Yang Y, Jin M. Patent WO2018177324 (A1); PCT/CN2018/080858. 2018
|
[74] |
Liu J, Song N, Yang Y. Patent WO2018090950 (A1); PCT/CN2017/111310. 2018
|
[75] |
Xu T, Dong Y, Wang P. Patent US 20180291103 (A1); PCT/CN2016/092679. 2017
|
[76] |
Wu C. Patent US 10266608 (B2); PCT/US2014/072336. 2019
|
[77] |
Eckelman B, Timmer JC, Hata C, Jones KS, Hussain A, Razai AS, Becklund B, Pandit R, Kaplan M, Rason L, Deveraux Q, Eckelman BP, Timmer JC, Hata C, Jones KS, Hussain A, Razai AS, Becklund B, Pandit R, Kaplan M, Rascon L, Deveraux Q. Patent US 20170198050 (A1); PCT/US2017/013040. 2017
|
[78] |
Kong J, Ye Y, Zhou P, Huang Y, Kong Q, Yang S, Xu L, Zhang K, Zhang K, Wang S. Patent US 20190284279 (A1); PCT/CN2018/085397. 2019
|
[79] |
Li B, Xia Y, Wang ZM, Zhang P. Patent US 20190185569 (A1); PCT/CN2017/098466. 2019
|
[80] |
Gao Z, TAN P, Kovacevich B, Renshaw B, Adamo J, Mak SA, Zhuo S, Chen L. Patent WO2016106157 (A1); PCT/US2015/066951. 2015
|
[81] |
LaMotte-Mohs R, Shah K, Smith D, Gorlatov S, Ciccarone V, Tamura J, Li H, Rillema J, Licea M. MGD013, a bispecific PD-1 X LAG-3 dual affinity re-targeting (DARTs) protein with T-cell immunomodulatory activity for cancer treatment. Cancer Res 2016; 76 (14 Supplement): 3217–3217
CrossRef
Google scholar
|
[82] |
Gu J, Luo X, Tao W. Patent CN 201880004344.6A; PCT/CN2018/086451. 2018
|
[83] |
Tian W, Li S. Patent WO201816650; PCT/CN2018/079187. 2018
|
[84] |
Huang Y, Zhang F, Xi G. Patent WO2019109357; PCT/CN2017/115323. 2019
|
[85] |
Hinner MJ, Aiba RSB, Wiedenmann A, Schlosser C, Allersdorfer A, Matschiner G, Rothe C, Moebius U, Kohrt HE, Olwill SA. Costimulatory T cell engagement via a novel bispecific anti-CD137/anti-HER2 protein. J Immunother Cancer 2015; 3(Suppl 2): 187
CrossRef
Google scholar
|
[86] |
Chames P, Baty D. Bispecific antibodies for cancer therapy. Curr Opin Drug Discov Devel 2009; 12(2): 276–283
Pubmed
|
[87] |
Poole RM. Pembrolizumab: first global approval. Drugs 2014; 74(16): 1973–1981
CrossRef
Pubmed
Google scholar
|
[88] |
Markham A. Atezolizumab: first global approval. Drugs 2016; 76(12): 1227–1232
CrossRef
Pubmed
Google scholar
|
[89] |
Kim ES. Avelumab: first global approval. Drugs 2017; 77(8): 929–937
CrossRef
Pubmed
Google scholar
|
[90] |
Syed YY. Durvalumab: first global approval. Drugs 2017; 77(12): 1369–1376
CrossRef
Pubmed
Google scholar
|
[91] |
Osipov A, Zaidi N, Laheru DA. Dual checkpoint inhibition in pancreatic cancer: revealing the limitations of synergy and the potential of novel combinations. JAMA Oncol 2019; 5(10): 1438–1439
CrossRef
Pubmed
Google scholar
|
[92] |
Reck M, Borghaei H, O’Byrne KJ. Nivolumab plus ipilimumab in non-small-cell lung cancer. Future Oncol 2019; 15(19): 2287–2302
CrossRef
Pubmed
Google scholar
|
[93] |
Winer A, Ghatalia P, Bubes N, Anari F, Varshavsky A, Kasireddy V, Liu Y, El-Deiry WS. Dual checkpoint inhibition with ipilimumab plus nivolumab after progression on sequential PD-1/PDL-1 inhibitors pembrolizumab and atezolizumab in a patient with Lynch syndrome, metastatic colon, and localized urothelial cancer. Oncologist 2019; 24(11): 1416–1419
CrossRef
Pubmed
Google scholar
|
[94] |
Hassel JC, Heinzerling L, Aberle J, Bähr O, Eigentler TK, Grimm MO, Grünwald V, Leipe J, Reinmuth N, Tietze JK, Trojan J, Zimmer L, Gutzmer R. Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): evaluation and management of adverse drug reactions. Cancer Treat Rev 2017; 57: 36–49
CrossRef
Pubmed
Google scholar
|
[95] |
Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol 2012; 24(2): 207–212
CrossRef
Pubmed
Google scholar
|
[96] |
Hugo W, Zaretsky JM, Sun L, Song C, Moreno BH, Hu-Lieskovan S, Berent-Maoz B, Pang J, Chmielowski B, Cherry G, Seja E, Lomeli S, Kong X, Kelley MC, Sosman JA, Johnson DB, Ribas A, Lo RS. Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell 2016; 165(1): 35–44
CrossRef
Pubmed
Google scholar
|
[97] |
Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, Lindeman N, Gale CM, Zhao X, Christensen J, Kosaka T, Holmes AJ, Rogers AM, Cappuzzo F, Mok T, Lee C, Johnson BE, Cantley LC, Jänne PA. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 2007; 316(5827): 1039–1043
CrossRef
Pubmed
Google scholar
|
[98] |
Turke AB, Zejnullahu K, Wu YL, Song Y, Dias-Santagata D, Lifshits E, Toschi L, Rogers A, Mok T, Sequist L, Lindeman NI, Murphy C, Akhavanfard S, Yeap BY, Xiao Y, Capelletti M, Iafrate AJ, Lee C, Christensen JG, Engelman JA, Jänne PA. Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell 2010; 17(1): 77–88
CrossRef
Pubmed
Google scholar
|
[99] |
Yano S, Yamada T, Takeuchi S, Tachibana K, Minami Y, Yatabe Y, Mitsudomi T, Tanaka H, Kimura T, Kudoh S, Nokihara H, Ohe Y, Yokota J, Uramoto H, Yasumoto K, Kiura K, Higashiyama M, Oda M, Saito H, Yoshida J, Kondoh K, Noguchi M. Hepatocyte growth factor expression in EGFR mutant lung cancer with intrinsic and acquired resistance to tyrosine kinase inhibitors in a Japanese cohort. J Thorac Oncol 2011; 6(12): 2011–2017
CrossRef
Pubmed
Google scholar
|
[100] |
van Lengerich B, Agnew C, Puchner EM, Huang B, Jura N. EGF and NRG induce phosphorylation of HER3/ERBB3 by EGFR using distinct oligomeric mechanisms. Proc Natl Acad Sci USA 2017; 114(14): E2836–E2845
CrossRef
Pubmed
Google scholar
|
[101] |
Mujoo K, Choi BK, Huang Z, Zhang N, An Z. Regulation of ERBB3/HER3 signaling in cancer. Oncotarget 2014; 5(21): 10222–10236
CrossRef
Pubmed
Google scholar
|
[102] |
Tian W, Li S, Chen D, Liang G, Zhang L, Zhang W, Tu X, Peng L, Weng J, Zhao G. Preclinical development of a bispecific antibody-trap selectively targeting CD47 and CD20 for the treatment of B cell lineage cancer. Cancer Res 2019; 79(13 Suppl): Abstract nr 545,
CrossRef
Google scholar
|
[103] |
Robert B, Dorvillius M, Buchegger F, Garambois V, Mani JC, Pugnières M, Mach JP, Pèlegrin A. Tumor targeting with newly designed biparatopic antibodies directed against two different epitopes of the carcinoembryonic antigen (CEA). Int J Cancer 1999; 81(2): 285–291
CrossRef
Pubmed
Google scholar
|
[104] |
Wei H, Cai H, Jin Y, Wang P, Zhang Q, Lin Y, Wang W, Cheng J, Zeng N, Xu T, Zhou A. Structural basis of a novel heterodimeric Fc for bispecific antibody production. Oncotarget 2017; 8(31): 51037–51049
CrossRef
Pubmed
Google scholar
|
[105] |
Li F, Zhang B, Ye P, Zhao J, Huang S, Jin C.Bispecific anti-HER2 antibody. 2017,
|
[106] |
Center for Drug Evaluation of the National Medical Products Authority. http://www.cde.org.cn/ (accessed August 31st, 2020)
|
[107] |
Li B, Xia Y, Wang Z M, Zhang P. Patent MX2019002254 (A). 2019
|
[108] |
Du X, Liu M, Su J, Zhang P, Tang F, Ye P, Devenport M, Wang X, Zhang Y, Liu Y, Zheng P. Uncoupling therapeutic from immunotherapy-related adverse effects for safer and effective anti-CTLA-4 antibodies in CTLA4 humanized mice. Cell Res 2018; 28(4): 433–447
CrossRef
Pubmed
Google scholar
|
[109] |
Du X, Tang F, Liu M, Su J, Zhang Y, Wu W, Devenport M, Lazarski CA, Zhang P, Wang X, Ye P, Wang C, Hwang E, Zhu T, Xu T, Zheng P, Liu Y. A reappraisal of CTLA-4 checkpoint blockade in cancer immunotherapy. Cell Res 2018; 28(4): 416–432
CrossRef
Pubmed
Google scholar
|
[110] |
Liu Y, Zheng P. Preserving the CTLA-4 checkpoint for safer and more effective cancer immunotherapy. Trends Pharmacol Sci 2020; 41(1): 4–12
CrossRef
Pubmed
Google scholar
|
[111] |
Duell J, Lurati S, Dittrich M, Bedke T, Pule M, Einsele H, Rossig C, Topp M S. First generation chimeric antigen receptor display functional defects in key signal pathways upon antigen stimulation. Blood 2010; 116(21):2088-
CrossRef
Google scholar
|
[112] |
Carpenito C, Milone MC, Hassan R, Simonet JC, Lakhal M, Suhoski MM, Varela-Rohena A, Haines KM, Heitjan DF, Albelda SM, Carroll RG, Riley JL, Pastan I, June CH. Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains. Proc Natl Acad Sci USA 2009; 106(9): 3360–3365
CrossRef
Pubmed
Google scholar
|
[113] |
June CH, O’Connor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR T cell immunotherapy for human cancer. Science 2018; 359(6382): 1361–1365
CrossRef
Pubmed
Google scholar
|
[114] |
Prasad V. Tisagenlecleucel—the first approved CAR-T-cell therapy: implications for payers and policy makers. Nat Rev Clin Oncol 2018; 15(1): 11–12
CrossRef
Pubmed
Google scholar
|
[115] |
Bouchkouj N, Kasamon YL, de Claro RA, George B, Lin X, Lee S, Blumenthal GM, Bryan W, McKee AE, Pazdur R. FDA approval summary: axicabtagene ciloleucel for relapsed or refractory large B-cell lymphoma. Clin Cancer Res 2019; 25(6): 1702–1708
CrossRef
Pubmed
Google scholar
|
[116] |
Voelker R. CAR-T therapy is approved for mantle cell lymphoma. JAMA 2020; 324(9): 832
Pubmed
|
[117] |
Mullard A. FDA approves fourth CAR-T cell therapy. Nat Rev Drug Discov 2021; 20(3): 166
Pubmed
|
[118] |
Ramos CA, Grover NS, Beaven AW, Lulla PD, Wu MF, Ivanova A, Wang T, Shea TC, Rooney CM, Dittus C, Park SI, Gee AP, Eldridge PW, McKay KL, Mehta B, Cheng CJ, Buchanan FB, Grilley BJ, Morrison K, Brenner MK, Serody JS, Dotti G, Heslop HE, Savoldo B. Anti-CD30 CAR-T cell therapy in relapsed and refractory Hodgkin lymphoma. J Clin Oncol 2020; 38(32): 3794–3804
CrossRef
Pubmed
Google scholar
|
[119] |
Huang R, Li X, He Y, Zhu W, Gao L, Liu Y, Gao L, Wen Q, Zhong JF, Zhang C, Zhang X. Recent advances in CAR-T cell engineering. J Hematol Oncol 2020; 13(1): 86
CrossRef
Pubmed
Google scholar
|
[120] |
Liu Y, Guo Y, Wu Z, Feng K, Tong C, Wang Y, Dai H, Shi F, Yang Q, Han W. Anti-EGFR chimeric antigen receptor-modified T cells in metastatic pancreatic carcinoma: a phase I clinical trial. Cytotherapy 2020; 22(10): 573–580
CrossRef
Pubmed
Google scholar
|
[121] |
Cutmore LC, Brown NF, Raj D, Chauduri S, Wang P, Maher J, Wang Y, Lemoine NR, Marshall JF. Pancreatic Cancer UK Grand Challenge: developments and challenges for effective CAR T cell therapy for pancreatic ductal adenocarcinoma. Pancreatology 2020; 20(3): 394–408
CrossRef
Pubmed
Google scholar
|
[122] |
Depil S, Duchateau P, Grupp SA, Mufti G, Poirot L. ‘Off-the-shelf’ allogeneic CAR T cells: development and challenges. Nat Rev Drug Discov 2020; 19(3): 185–199
CrossRef
Pubmed
Google scholar
|
[123] |
Cutmore LC, Marshall JF. Current perspectives on the use of off the Shelf CAR-T/NK cells for the treatment of cancer. Cancers (Basel) 2021; 13(8): 1926
CrossRef
Pubmed
Google scholar
|
[124] |
Capsomidis A, Benthall G, Van Acker HH, Fisher J, Kramer AM, Abeln Z, Majani Y, Gileadi T, Wallace R, Gustafsson K, Flutter B, Anderson J. Chimeric antigen receptor-engineered human gamma delta T cells: enhanced cytotoxicity with retention of cross presentation. Mol Ther 2018; 26(2): 354–365
CrossRef
Pubmed
Google scholar
|
[125] |
Torikai H, Reik A, Liu PQ, Zhou Y, Zhang L, Maiti S, Huls H, Miller JC, Kebriaei P, Rabinovich B, Lee DA, Champlin RE, Bonini C, Naldini L, Rebar EJ, Gregory PD, Holmes MC, Cooper LJ. A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR. Blood 2012; 119(24): 5697–5705
CrossRef
Pubmed
Google scholar
|
[126] |
Melenhorst JJ, Leen AM, Bollard CM, Quigley MF, Price DA, Rooney CM, Brenner MK, Barrett AJ, Heslop HE. Allogeneic virus-specific T cells with HLA alloreactivity do not produce GVHD in human subjects. Blood 2010; 116(22): 4700–4702
CrossRef
Pubmed
Google scholar
|
[127] |
Kochenderfer JN, Dudley ME, Carpenter RO, Kassim SH, Rose JJ, Telford WG, Hakim FT, Halverson DC, Fowler DH, Hardy NM, Mato AR, Hickstein DD, Gea-Banacloche JC, Pavletic SZ, Sportes C, Maric I, Feldman SA, Hansen BG, Wilder JS, Blacklock-Schuver B, Jena B, Bishop MR, Gress RE, Rosenberg SA. Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood 2013; 122(25): 4129–4139
CrossRef
Pubmed
Google scholar
|
[128] |
Guo F, Cui J. CAR-T in cancer treatment: develop in self-optimization, win-win in cooperation. Cancers (Basel) 2021; 13(8): 1955
CrossRef
Pubmed
Google scholar
|
[129] |
Hu J, Sun C, Bernatchez C, Xia X, Hwu P, Dotti G, Li S. T-cell homing therapy for reducing regulatory T cells and preserving effector T-cell function in large solid tumors. Clin Cancer Res 2018; 24(12): 2920–2934
CrossRef
Pubmed
Google scholar
|
[130] |
Murty S, Haile ST, Beinat C, Aalipour A, Alam IS, Murty T, Shaffer TM, Patel CB, Graves EE, Mackall CL, Gambhir SS. Intravital imaging reveals synergistic effect of CAR T-cells and radiation therapy in a preclinical immunocompetent glioblastoma model. OncoImmunology 2020; 9(1): 1757360
CrossRef
Pubmed
Google scholar
|
[131] |
Grosser R, Cherkassky L, Chintala N, Adusumilli PS. Combination immunotherapy with CAR T cells and checkpoint blockade for the treatment of solid tumors. Cancer Cell 2019; 36(5): 471–482
CrossRef
Pubmed
Google scholar
|
[132] |
Lee YG, Marks I, Srinivasarao M, Kanduluru AK, Mahalingam SM, Liu X, Chu H, Low PS. Use of a single CAR T cell and several bispecific adapters facilitates eradication of multiple antigenically different solid tumors. Cancer Res 2019; 79(2): 387–396
CrossRef
Pubmed
Google scholar
|
[133] |
Driouk L, Gicobi JK, Kamihara Y, Rutherford K, Dranoff G, Ritz J, Baumeister SHC. Chimeric antigen receptor T cells targeting NKG2D-ligands show robust efficacy against acute myeloid leukemia and T-cell acute lymphoblastic leukemia. Front Immunol 2020; 11: 580328
CrossRef
Pubmed
Google scholar
|
[134] |
Caruana I, Weber G, Ballard BC, Wood MS, Savoldo B, Dotti G. K562-derived whole-cell vaccine enhances antitumor responses of CAR-redirected virus-specific cytotoxic T lymphocytes in vivo. Clin Cancer Res 2015; 21(13): 2952–2962
CrossRef
Pubmed
Google scholar
|
[135] |
Bommareddy PK, Shettigar M, Kaufman HL. Integrating oncolytic viruses in combination cancer immunotherapy. Nat Rev Immunol 2018; 18(8): 498–513
CrossRef
Pubmed
Google scholar
|
[136] |
Hu Z, Ott PA, Wu CJ. Towards personalized, tumour-specific, therapeutic vaccines for cancer. Nat Rev Immunol 2018; 18(3): 168–182
CrossRef
Pubmed
Google scholar
|
[137] |
Parkhurst MR, Yang JC, Langan RC, Dudley ME, Nathan DA, Feldman SA, Davis JL, Morgan RA, Merino MJ, Sherry RM, Hughes MS, Kammula US, Phan GQ, Lim RM, Wank SA, Restifo NP, Robbins PF, Laurencot CM, Rosenberg SA. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol Ther 2011; 19(3): 620–626
CrossRef
Pubmed
Google scholar
|
[138] |
Blass E, Ott PA. Advances in the development of personalized neoantigen-based therapeutic cancer vaccines. Nat Rev Clin Oncol 2021; 18(4): 215–229
CrossRef
Pubmed
Google scholar
|
[139] |
Ott PA, Hu Z, Keskin DB, Shukla SA, Sun J, Bozym DJ, Zhang W, Luoma A, Giobbie-Hurder A, Peter L, Chen C, Olive O, Carter TA, Li S, Lieb DJ, Eisenhaure T, Gjini E, Stevens J, Lane WJ, Javeri I, Nellaiappan K, Salazar AM, Daley H, Seaman M, Buchbinder EI, Yoon CH, Harden M, Lennon N, Gabriel S, Rodig SJ, Barouch DH, Aster JC, Getz G, Wucherpfennig K, Neuberg D, Ritz J, Lander ES, Fritsch EF, Hacohen N, Wu CJ. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 2017; 547(7662): 217–221
CrossRef
Pubmed
Google scholar
|
[140] |
Hu Z, Leet DE, Allesøe RL, Oliveira G, Li S, Luoma AM, Liu J, Forman J, Huang T, Iorgulescu JB, Holden R, Sarkizova S, Gohil SH, Redd RA, Sun J, Elagina L, Giobbie-Hurder A, Zhang W, Peter L, Ciantra Z, Rodig S, Olive O, Shetty K, Pyrdol J, Uduman M, Lee PC, Bachireddy P, Buchbinder EI, Yoon CH, Neuberg D, Pentelute BL, Hacohen N, Livak KJ, Shukla SA, Olsen LR, Barouch DH, Wucherpfennig KW, Fritsch EF, Keskin DB, Wu CJ, Ott PA. Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma. Nat Med 2021; 27(3): 515–525
CrossRef
Pubmed
Google scholar
|
[141] |
Keskin DB, Anandappa AJ, Sun J, Tirosh I, Mathewson ND, Li S, Oliveira G, Giobbie-Hurder A, Felt K, Gjini E, Shukla SA, Hu Z, Li L, Le PM, Allesøe RL, Richman AR, Kowalczyk MS, Abdelrahman S, Geduldig JE, Charbonneau S, Pelton K, Iorgulescu JB, Elagina L, Zhang W, Olive O, McCluskey C, Olsen LR, Stevens J, Lane WJ, Salazar AM, Daley H, Wen PY, Chiocca EA, Harden M, Lennon NJ, Gabriel S, Getz G, Lander ES, Regev A, Ritz J, Neuberg D, Rodig SJ, Ligon KL, Suvà ML, Wucherpfennig KW, Hacohen N, Fritsch EF, Livak KJ, Ott PA, Wu CJ, Reardon DA. Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature 2019; 565(7738): 234–239
CrossRef
Pubmed
Google scholar
|
[142] |
Ott PA, Hu-Lieskovan S, Chmielowski B, Govindan R, Naing A, Bhardwaj N, Margolin K, Awad MM, Hellmann MD, Lin JJ, Friedlander T, Bushway ME, Balogh KN, Sciuto TE, Kohler V, Turnbull SJ, Besada R, Curran RR, Trapp B, Scherer J, Poran A, Harjanto D, Barthelme D, Ting YS, Dong JZ, Ware Y, Huang Y, Huang Z, Wanamaker A, Cleary LD, Moles MA, Manson K, Greshock J, Khondker ZS, Fritsch E, Rooney MS, DeMario M, Gaynor RB, Srinivasan L. A phase Ib trial of personalized neoantigen therapy plus anti-PD-1 in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. Cell 2020; 183(2): 347–362.e24PMID:33064988
CrossRef
Google scholar
|
[143] |
Lindskog M, Laurell A, Kjellman A, Melichar B, Niezabitowski J, Maroto P, Zieliński H, Villacampa F, Bigot P, Bajory Z.A randomized phase II study with ilixadencel, a cell-based immune primer, plus sunitinib versus sunitinib alone in synchronous metastatic renal cell carcinoma. J Clin Oncol 2020; 38(5_suppl):11
CrossRef
Google scholar
|
[144] |
Tanyi JL, Bobisse S, Ophir E, Tuyaerts S, Roberti A, Genolet R, Baumgartner P, Stevenson BJ, Iseli C, Dangaj D, Czerniecki B, Semilietof A, Racle J, Michel A, Xenarios I, Chiang C, Monos DS, Torigian DA, Nisenbaum HL, Michielin O, June CH, Levine BL, Powell DJ Jr, Gfeller D, Mick R, Dafni U, Zoete V, Harari A, Coukos G, Kandalaft LE. Personalized cancer vaccine effectively mobilizes antitumor T cell immunity in ovarian cancer. Sci Transl Med 2018; 10(436): eaao5931
CrossRef
Pubmed
Google scholar
|
[145] |
Moynihan KD, Opel CF, Szeto GL, Tzeng A, Zhu EF, Engreitz JM, Williams RT, Rakhra K, Zhang MH, Rothschilds AM, Kumari S, Kelly RL, Kwan BH, Abraham W, Hu K, Mehta NK, Kauke MJ, Suh H, Cochran JR, Lauffenburger DA, Wittrup KD, Irvine DJ. Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses. Nat Med 2016; 22(12): 1402–1410
CrossRef
Pubmed
Google scholar
|
[146] |
Chau I, Haag G, Rahma O, Macarulla T, McCune S, Yardley D, Solomon B, Johnson M, Vidal G, Schmid P, Argiles G, Dimick K, Mahrus S, Abdullah H, He X, Sayyed P, Barak H, Bleul C, Cha E, Drakaki A. MORPHEUS: A phase Ib/II umbrella study platform evaluating the safety and efficacy of multiple cancer immunotherapy (CIT)-based combinations in different tumour types. Ann Oncol 2018; 29(suppl_8): 439–440
CrossRef
Google scholar
|
[147] |
Simonsen KL, Fracasso PM, Bernstein SH, Wind-Rotolo M, Gupta M, Comprelli A, Reilly TP, Cassidy J. The Fast Real-time Assessment of Combination Therapies in Immuno-ONcology (FRACTION) program: innovative, high-throughput clinical screening of immunotherapies. Eur J Cancer 2018; 103: 259–266
CrossRef
Pubmed
Google scholar
|
[148] |
Redman JM, Steinberg SM, Gulley JL. Quick efficacy seeking trial (QuEST1): a novel combination immunotherapy study designed for rapid clinical signal assessment metastatic castration-resistant prostate cancer. J Immunother Cancer 2018; 6(1): 91
CrossRef
Pubmed
Google scholar
|
[149] |
Tang J, Shalabi A, Hubbard-Lucey VM. Comprehensive analysis of the clinical immuno-oncology landscape. Ann Oncol 2018; 29(1): 84–91
CrossRef
Pubmed
Google scholar
|
[150] |
Monk BJ, Brady MF, Aghajanian C, Lankes HA, Rizack T, Leach J, Fowler JM, Higgins R, Hanjani P, Morgan M, Edwards R, Bradley W, Kolevska T, Foukas P, Swisher EM, Anderson KS, Gottardo R, Bryan JK, Newkirk M, Manjarrez KL, Mannel RS, Hershberg RM, Coukos G. A phase 2, randomized, double-blind, placebo-controlled study of chemo-immunotherapy combination using motolimod with pegylated liposomal doxorubicin in recurrent or persistent ovarian cancer: a Gynecologic Oncology Group partners study. Ann Oncol 2017; 28(5): 996–1004
CrossRef
Pubmed
Google scholar
|
[151] |
Yu S, Yi M, Qin S, Wu K. Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity. Mol Cancer 2019; 18(1): 125
CrossRef
Pubmed
Google scholar
|
[152] |
Levy BP, Giaccone G, Besse B, Felip E, Garassino MC, Domine Gomez M, Garrido P, Piperdi B, Ponce-Aix S, Menezes D, MacBeth KJ, Risueño A, Slepetis R, Wu X, Fandi A, Paz-Ares L. Randomised phase 2 study of pembrolizumab plus CC-486 versus pembrolizumab plus placebo in patients with previously treated advanced non-small cell lung cancer. Eur J Cancer 2019; 108: 120–128
CrossRef
Pubmed
Google scholar
|
[153] |
Mijalis AJ, Thomas DA 3rd, Simon MD, Adamo A, Beaumont R, Jensen KF, Pentelute BL. A fully automated flow-based approach for accelerated peptide synthesis. Nat Chem Biol 2017; 13(5): 464–466
CrossRef
Pubmed
Google scholar
|
/
〈 | 〉 |