CD70: An emerging target for integrated cancer diagnosis and therapy

Jiatao Hu , Jinxin Li , Bo Yang , Siyi Wang , Yi Bao , Yiren Yang , Kun Qiao , Fei Guo , Xinxin Gan , Linhui Wang

Clinical and Translational Medicine ›› 2025, Vol. 15 ›› Issue (7) : e70400

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Clinical and Translational Medicine ›› 2025, Vol. 15 ›› Issue (7) : e70400 DOI: 10.1002/ctm2.70400
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CD70: An emerging target for integrated cancer diagnosis and therapy

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Abstract

CD70, which is a ligand belonging to tumour necrosis factors, exhibits aberrant overexpression among multiple hematologic and solid malignancies and has drawn extensive research enthusiasm as a target to treat and diagnose cancers. CD70-targeted immuno-PET/CT is an emerging approach for cancer diagnosis, with the potential to improve tumour detection, assist disease staging, and monitor therapeutic response. CD70-targeted therapeutic approaches, involving antibody–drug conjugates, CAR-T, CAR-NK, and monoclonal antibodies, have shown encouraging activity in preclinical models and preliminary signals of efficacy in early clinical studies. In addition to these monotherapies, increasing efforts have focused on rational combination strategies that aim to enhance antitumor efficacy, reverse immune suppression, and overcome resistance. This review comprehensively summarizes the diagnostic and therapeutic advances in CD70-targeted strategies, discusses ongoing barriers, and outlines future directions to advance CD70-targeted imaging and therapeutic strategies through mechanistic research and clinical translation.

Keywords

CD70 / immuno-PET/CT / CAR-T / combination therapy / targeted therapy

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Jiatao Hu, Jinxin Li, Bo Yang, Siyi Wang, Yi Bao, Yiren Yang, Kun Qiao, Fei Guo, Xinxin Gan, Linhui Wang. CD70: An emerging target for integrated cancer diagnosis and therapy. Clinical and Translational Medicine, 2025, 15(7): e70400 DOI:10.1002/ctm2.70400

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References

[1]

Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024; 74: 229-263.

[2]

Liu J, Pandya P, Afshar S. Therapeutic advances in oncology. Int J Mol Sci. 2021; 22: 2008.

[3]

Liu B, Zhou H, Tan L, Siu KTH, Guan X. Exploring treatment options in cancer: tumor treatment strategies. Signal Transduct Target Ther. 2024; 9: 175.

[4]

Krishna S, Murray C, McInnes M, et al. CT imaging of solid renal masses: pitfalls and solutions. Clin Radiol. 2017; 72: 708-721.

[5]

Kim JH, Sun HY, Hwang J, et al. Diagnostic accuracy of contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging of small renal masses in real practice: sensitivity and specificity according to subjective radiologic interpretation. World J Surg Oncol. 2016; 14: 260.

[6]

Liu Y. The place of FDG PET/CT in renal cell carcinoma: value and limitations. Front Oncol. 2016; 6: 201.

[7]

Rahman WT, Wale DJ, Viglianti BL, et al. The impact of infection and inflammation in oncologic 18F-FDG PET/CT imaging. Biomed Pharmacother. 2019; 117: 109168.

[8]

Lakhani A, Khan SR, Bharwani N, et al. FDG PET/CT pitfalls in gynecologic and genitourinary oncologic imaging. Radiographics. 2017; 37: 577-594.

[9]

Ye F, Dewanjee S, Li Y, et al. Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer. Mol Cancer. 2023; 22: 105.

[10]

Yu S, Li A, Liu Q, et al. Chimeric antigen receptor T cells: a novel therapy for solid tumors. J Hematol OncolJ Hematol Oncol. 2017; 10: 78.

[11]

Bagchi S, Yuan R, Engleman EG. Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance. Annu Rev Pathol Mech Dis. 2021; 16: 223-249.

[12]

Wu D, Wang DC, Cheng Y, et al. Roles of tumor heterogeneity in the development of drug resistance: a call for precision therapy. Semin Cancer Biol. 2017; 42: 13-19.

[13]

Schoenfeld AJ, Hellmann MD. Acquired resistance to immune checkpoint inhibitors. Cancer Cell. 2020; 37: 443-455.

[14]

Zhou Y, Tao L, Qiu J, et al. Tumor biomarkers for diagnosis, prognosis and targeted therapy. Signal Transduct Target Ther. 2024; 9: 132.

[15]

Liu Z, Wang S, Dong D, et al. The applications of radiomics in precision diagnosis and treatment of oncology: opportunities and challenges. Theranostics. 2019; 9: 1303-1322.

[16]

Lambin P, Leijenaar RT, Deist TM, et al. Radiomics: the bridge between medical imaging and personalized medicine. Nat Rev Clin Oncol. 2017; 14: 749-762.

[17]

Grewal IS. CD70 as a therapeutic target in human malignancies. Expert Opin Ther Targets. 2008; 12: 341-351.

[18]

Borst J, Hendriks J, Xiao Y. CD27 and CD70 in T cell and B cell activation. Curr Opin Immunol. 2005; 17: 275-281.

[19]

Nolte MA, Van Olffen RW, Van Gisbergen KPJM, Van Lier RAW. Timing and tuning of CD27-CD70 interactions: the impact of signal strength in setting the balance between adaptive responses and immunopathology. Immunol Rev. 2009; 229: 216-231.

[20]

Flieswasser T, Van den Eynde A, Van Audenaerde J, et al. The CD70-CD27 axis in oncology: the new kids on the block. J Exp Clin Cancer Res. 2022; 41: 12.

[21]

Jacobs J, Deschoolmeester V, Zwaenepoel K, et al. CD70: an emerging target in cancer immunotherapy. Pharmacol Ther. 2015; 155: 1-10.

[22]

Kashima J, Hishima T, Okuma Y, et al. CD70 in thymic squamous cell carcinoma: potential diagnostic markers and immunotherapeutic targets. Front Oncol. 2022; 11: 808396.

[23]

Jilaveanu LB, Sznol J, Aziz SA, Duchen D, Kluger HM, Camp RL. CD70 expression patterns in renal cell carcinoma. Hum Pathol. 2012; 43: 1394-1399.

[24]

Rav E, Maegawa S, Gopalakrishnan V, Gordon N. Overview of CD70 as a potential therapeutic target for osteosarcoma. J Immunol. 2023; 211: 1067-1072.

[25]

Kumar S, Mahendiran S, Nair RS, et al. A mechanistic, functional, and clinical perspective on targeting CD70 in cancer. Cancer Lett. 2025; 611: 217428.

[26]

Zhang X, Hong B, Yu W, et al. Comprehensive pan-cancer analysis reveals CD70 as a promising therapeutic target and biomarker in clear cell renal cell carcinoma. Int J Biol Macromol. 2025; 307: 142079.

[27]

Ruf M, Mittmann C, Nowicka AM, et al. pVHL/HIF-regulated CD70 expression is associated with infiltration of CD27+ lymphocytes and increased serum levels of soluble CD27 in clear cell renal cell carcinoma. Clin Cancer Res. 2015; 21: 889-898.

[28]

Wei W, Grünwald V, Herrmann K. CD70-targeted cancer theranostics: progress and challenges. Med. 2025: 100671.

[29]

Gong L, Luo J, Zhang Y, et al. Nasopharyngeal carcinoma cells promote regulatory T cell development and suppressive activity via CD70-CD27 interaction. Nat Commun. 2023; 14: 1912.

[30]

Ortiz-Cuaran S, Swalduz A, Foy J, et al. Epithelial-to-mesenchymal transition promotes immune escape by inducing CD70 in non-small cell lung cancer. Eur J Cancer. 2022; 169: 106-122.

[31]

Nilsson MB, Yang Y, Heeke S, et al. CD70 is a therapeutic target upregulated in EMT-associated EGFR tyrosine kinase inhibitor resistance. Cancer Cell. 2023; 41: 340-355.e6.

[32]

Seyfrid M, Maich WT, Shaikh MV, et al. CD70 as an actionable immunotherapeutic target in recurrent glioblastoma and its microenvironment. J Immunother Cancer. 2022; 10: e003289.

[33]

Diegmann J, Junker K, Loncarevic IF, Michel S, Schimmel B, von Eagelinq F. Immune escape for renal cell carcinoma: cD70 mediates apoptosis in lymphocytes. Neoplasia. 2006; 8: 933-938.

[34]

Riether C, Schürch CM, Bührer ED, et al. CD70/CD27 signaling promotes blast stemness and is a viable therapeutic target in acute myeloid leukemia. J Exp Med. 2017; 214: 359-380.

[35]

Kong F, Ye Q, Xiong Y. Comprehensive analysis of prognosis and immune function of CD70-CD27 signaling axis in pan-cancer. Funct Integr Genomics. 2023; 23: 48.

[36]

Wajant H. Therapeutic targeting of CD70 and CD27. Expert Opin Ther Targets. 2016; 20: 959-973.

[37]

Guo S, Lei W, Jin X, et al. CD70-specific CAR NK cells expressing IL-15 for the treatment of CD19-negative B-cell malignancy. Blood Adv. 2024; 8: 2635-2645.

[38]

Jin L, Ge H, Long Y, et al. CD70, a novel target of CAR T-cell therapy for gliomas. Neuro Oncol. 2018; 20: 55-65.

[39]

Park YP, Jin L, Bennett KB, et al. CD70 as a target for chimeric antigen receptor T cells in head and neck squamous cell carcinoma. Oral Oncol. 2018; 78: 145-150.

[40]

Wu Q, Wu Y, Zhang Y, et al. ImmunoPET/CT imaging of clear cell renal cell carcinoma with [18F]RCCB6: a first-in-human study. Eur J Nucl Med Mol Imaging. 2024; 51: 2444-2457.

[41]

Wei W, Rosenkrans ZT, Liu J, Huang G, Luo Q, Cai W. ImmunoPET: concept, design, and applications. Chem Rev. 2020; 120: 3787-3851.

[42]

Pang Y, Zhao L, Meng T, et al. PET imaging of fibroblast activation protein in various types of cancer Using68 ga-FAP-2286: comparison with18 F-FDG and68 ga-FAPI-46 in a single-center, prospective study. J Nucl Med. 2023; 64: 386-394.

[43]

Kline B, Yadav S, Seo Y, et al. 68 ga-FAP-2286 PET of solid tumors: biodistribution, dosimetry, and comparison with18 F-FDG. J Nucl Med. 2024; 65: 938-943.

[44]

Duan X, Xia L, Zhang Z, et al. First-in-human study of the radioligand 68Ga-N188 targeting nectin-4 for PET/CT imaging of advanced urothelial carcinoma. Clin Cancer Res Off J Am Assoc Cancer Res. 2023; 29: 3395-3407.

[45]

Zhang J, Duan X, Chen X, et al. Translational PET imaging of nectin-4 expression in multiple different cancers with68 ga-N188. J Nucl Med. 2024; 65: 12S-18S.

[46]

Dewulf J, Flieswasser T, Delahaye T, et al. Site-specific 68Ga-labeled nanobody for PET imaging of CD70 expression in preclinical tumor models. EJNMMI Radiopharm Chem. 2023; 8: 8.

[47]

Wu S, Wu Q, Liu J, Zhang J, Wei W. [18F]RCCB6 immunoPET/CT detects primary clear cell renal cell carcinoma. Eur J Nucl Med Mol Imaging. 2024; 52: 1944-1945.

[48]

Wu Q, Wu Y, Zhang Y, et al. [18F]RCCB6 immuno-positron emission tomography/computed tomography for postoperative surveillance in clear cell renal cell carcinoma: a pilot clinical study. Eur Urol. 2024; 86(4): 372-374.

[49]

Zhou X, Wu Q, Zhai W, et al. CD70-targeted immuno-PET/CT imaging of clear cell renal cell carcinoma: a translational study. J Nucl Med. 2024; 65(12): 1891-1898.

[50]

Chen K, Conti PS. Target-specific delivery of peptide-based probes for PET imaging. Adv Drug Deliv Rev. 2010; 62: 1005-1022.

[51]

Hassanzadeh L, Chen S, Veedu RN. Radiolabeling of nucleic acid aptamers for highly sensitive disease-specific molecular imaging. Pharm Basel Switz. 2018; 11: 106.

[52]

Schwenck J, Sonanini D, Cotton JM, et al. Advances in PET imaging of cancer. Nat Rev Cancer. 2023; 23: 474-490.

[53]

Paul S, Konig MF, Pardoll DM, et al. Cancer therapy with antibodies. Nat Rev Cancer. 2024; 24: 399-426.

[54]

Breedveld FC. Therapeutic monoclonal antibodies. Lancet Lond Engl. 2000; 355: 735-740.

[55]

Silence K, Dreier T, Moshir M, et al. ARGX-110, a highly potent antibody targeting CD70, eliminates tumors via both enhanced ADCC and immune checkpoint blockade. mAbs. 2014; 6: 523-532.

[56]

Aftimos P, Rolfo C, Rottey S, et al. Phase I dose-escalation study of the anti-CD70 antibody ARGX-110 in advanced malignancies. Clin Cancer Res. 2017; 23: 6411-6420.

[57]

Leupin N, Zinzani PL, Morschhauser F, et al. Cusatuzumab for treatment of CD70-positive relapsed or refractory cutaneous T-cell lymphoma. Cancer. 2022; 128: 1004-1014.

[58]

De Meulenaere A, Vermassen T, Creytens D, et al. An open-label, nonrandomized, phase ib feasibility study of cusatuzumab in patients with nasopharyngeal carcinoma. Clin Transl Sci. 2021; 14(6): 2300-2313.

[59]

Li S, Chen D, Guo H, et al. The novel high-affinity humanized antibody IMM40H targets CD70, eliminates tumors via fc-mediated effector functions, and interrupts CD70/CD27 signaling. Front Oncol. 2023; 13: 1240061.

[60]

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: 93.

[61]

Jin Y, Schladetsch MA, Huang X, Balunas MJ, Wiemer AJ. Stepping forward in antibody-drug conjugate development. Pharmacol Ther. 2022; 229: 107917.

[62]

Xi M, Zhu J, Zhang F, et al. Antibody-drug conjugates for targeted cancer therapy: recent advances in potential payloads. Eur J Med Chem. 2024; 276: 116709.

[63]

Birrer MJ, Moore KN, Betella I, Bates RC. Antibody-drug conjugate-based therapeutics: state of the science. J Natl Cancer Inst. 2019; 111: 538-549.

[64]

Nakae R, Matsuzaki S, Serada S, et al. CD70 antibody-drug conjugate as a potential therapeutic agent for uterine leiomyosarcoma. Am J Obstet Gynecol. 2021; 224: 197.e1-197.e23.

[65]

Shiomi M, Matsuzaki S, Serada S, et al. CD70 antibody-drug conjugate: a potential novel therapeutic agent for ovarian cancer. Cancer Sci. 2021; 112: 3655-3668.

[66]

Donaghy H. Effects of antibody, drug and linker on the preclinical and clinical toxicities of antibody-drug conjugates. mAbs. 2016; 8: 659-671.

[67]

Ryan MC, Kostner H, Gordon KA, et al. Targeting pancreatic and ovarian carcinomas using the auristatin-based anti-CD70 antibody-drug conjugate SGN-75. Br J Cancer. 2010; 103: 676-684.

[68]

Tannir NM, Forero-Torres A, Ramchandren R, et al. Phase I dose-escalation study of SGN-75 in patients with CD70-positive relapsed/refractory non-Hodgkin lymphoma or metastatic renal cell carcinoma. Invest New Drugs. 2014; 32: 1246-1257.

[69]

Owonikoko TK, Hussain A, Stadler WM, et al. First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70. Cancer Chemother Pharmacol. 2016; 77: 155-162.

[70]

Wu C, Wang L, Yang C, et al. Targeting CD70 in cutaneous T-cell lymphoma using an antibody-drug conjugate in patient-derived xenograft models. Blood Adv. 2022; 6: 2290-2302.

[71]

Phillips T, Barr PM, Park SI, et al. A phase 1 trial of SGN-CD70A in patients with CD70-positive diffuse large B cell lymphoma and mantle cell lymphoma. Invest New Drugs. 2019; 37: 297-306.

[72]

Pal SK, Forero-Torres A, Thompson JA, et al. A phase 1 trial of SGN-CD70A in patients with CD70-positive, metastatic renal cell carcinoma. Cancer. 2019; 125: 1124-1132.

[73]

Massard C, Soria J, Krauss J, et al. First-in-human study to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of the anti-CD27L antibody-drug conjugate AMG 172 in patients with relapsed/refractory renal cell carcinoma. Cancer Chemother Pharmacol. 2019; 83: 1057-1063.

[74]

Hafeez U, Parakh S, Gan HK, Scott AM. Antibody-drug conjugates for cancer therapy. Mol Basel, Switzrland. 2020; 25: 4764.

[75]

Phuna ZX, Kumar PA, Haroun E, Dutta D, Lim SH. Antibody-drug conjugates: principles and opportunities. Life Sci. 2024; 347: 122676.

[76]

Chen Y, Abila B, Mostafa Kamel Y. CAR-T: what is next?. Cancers. 2023; 15: 663.

[77]

Wang J, Wang L. CAR-T cell therapy: where are we now, and where are we heading?. Blood Sci. 2023; 5: 237-248.

[78]

Zang PD, Angeles A, Pal SK, CD70: An emerging anticancer target in renal cell carcinoma and beyond. (2024)

[79]

Wang Y, Wang S, Li N. Accelerating the clinical translation of CD70-targeted chimeric antigen receptor-based cell therapies in oncology: a comprehensive clinical investigation panorama analysis based on the trialtrove database. Cancer Lett. 2025; 614: 217510.

[80]

Wu G, Guo S, Luo Q, et al. Preclinical evaluation of CD70-specific CAR T cells targeting acute myeloid leukemia. Front Immunol. 2023; 14: 1093750.

[81]

Deng W, Chen P, Lei W, et al. CD70-targeting CAR-T cells have potential activity against CD19-negative B-cell lymphoma. Cancer Commun. 2021; 41: 925-929.

[82]

Wang QJ, Yu Z, Hanada K, et al. Preclinical evaluation of chimeric antigen receptors targeting CD70-expressing cancers. Clin Cancer Res. 2017; 23: 2267-2276.

[83]

Sauer T, Parikh K, Sharma S, et al. CD70-specific CAR T cells have potent activity against acute myeloid leukemia without HSC toxicity. Blood. 2021; 138: 318-330.

[84]

Yang M, Tang X, Zhang Z, et al. Tandem CAR-T cells targeting CD70 and B7-H3 exhibit potent preclinical activity against multiple solid tumors. Theranostics. 2020; 10: 7622-7634.

[85]

Sun S, Ding Z, Yang X, et al. Nanobody: a small antibody with big implications for tumor therapeutic strategy. Int J Nanomedicine. 2021; 16: 2337-2356.

[86]

Muyldermans S. Nanobodies: natural single-domain antibodies. Annu Rev Biochem. 2013; 82: 775-797.

[87]

Bao C, Gao Q, Li L, et al. The application of nanobody in CAR-T therapy. Biomolecules. 2021; 11: 238.

[88]

Safarzadeh Kozani P, Naseri A, Mirarefin SMJ, et al. Nanobody-based CAR-T cells for cancer immunotherapy. Biomark Res. 2022; 10: 24.

[89]

Nix MA, Wiita AP. Alternative target recognition elements for chimeric antigen receptor (CAR) T cells: beyond standard antibody fragments. Cytotherapy. 2024; 26: 729-738.

[90]

Jin B, Odongo S, Radwanska M, Magez S. NANOBODIES®: a review of diagnostic and therapeutic applications. Int J Mol Sci. 2023; 24: 5994.

[91]

Alexander E, Leong KW. Discovery of nanobodies: a comprehensive review of their applications and potential over the past five years. J Nanobiotechnology. 2024; 22: 661.

[92]

Xiong Q, Wang H, Shen Q, et al. The development of chimeric antigen receptor T-cells against CD70 for renal cell carcinoma treatment. J Transl Med. 2024; 22: 368.

[93]

Mansilla-Soto J, Eyquem J, Haubner S, et al. HLA-independent T cell receptors for targeting tumors with low antigen density. Nat Med. 2022; 28: 345-352.

[94]

Silva HJ, Martin G, Birocchi F, et al. CD70 CAR T cells secreting an anti-CD33/anti-CD3 dual targeting antibody overcome antigen heterogeneity in AML. Blood J. 2024.

[95]

Jiao C, Zvonkov E, Lai X, et al. 4SCAR2.0: a multi-CAR-T therapy regimen for the treatment of relapsed/refractory B cell lymphomas. Blood Cancer J. 2021; 11: 59.

[96]

Tu S, Zhou X, Guo Z, et al. CD19 and CD70 dual-target chimeric antigen receptor T-cell therapy for the treatment of relapsed and refractory primary central nervous system diffuse large B-cell lymphoma. Front Oncol. 2019; 9: 1350.

[97]

Adotévi O, Galaine J. Antitumor CAR T-cell screening platform: many are called, but few are chosen. Cancer Res. 2022; 82: 2517-2519.

[98]

Zhao J, Lin Q, Song Y, Liu D. Universal CARs, universal T cells, and universal CAR T cells. J Hematol OncolJ Hematol Oncol. 2018; 11: 132.

[99]

Wu Z, Wang Y, Jin X, Wang L. Universal CAR cell therapy: challenges and expanding applications. Transl Oncol. 2025; 51: 102147.

[100]

Panowski SH, Srinivasan S, Tan N, et al. Preclinical development and evaluation of allogeneic CAR T cells targeting CD70 for the treatment of renal cell carcinoma. Cancer Res. 2022; 82: 2610-2624.

[101]

Pal SK, Tran B, Haanen JB, et al. CD70-targeted allogeneic CAR T-cell therapy for advanced clear cell renal cell carcinoma. Cancer Discov. 2024; 14: 1176-1189.

[102]

Iyer SP, Sica RA, Ho PJ, et al. Safety and activity of CTX130, a CD70-targeted allogeneic CRISPR-Cas9-engineered CAR T-cell therapy, in patients with relapsed or refractory T-cell malignancies (COBALT-LYM): a single-arm, open-label, phase 1, dose-escalation study. Lancet Oncol. 2024.

[103]

Zhang Z, Zhao L, Huang T, et al. A self-activated and protective module enhances the preclinical performance of allogeneic anti-CD70 CAR-T cells. Front Immunol. 2025; 15: 1531294.

[104]

Braun T, Schrader A. Education and empowering special forces to eradicate secret defectors: immune system-based treatment approaches for mature T- and NK-cell malignancies. Cancers. 2023; 15: 2532.

[105]

De Munter S, Buhl JL, De Cock L, et al. Knocking out CD70 rescues CD70-specific NanoCAR T cells from antigen-induced exhaustion. Cancer Immunol Res. 2024; 12(9): 1236-1251.

[106]

Cheng J, Zhao Y, Hu H, et al. Revealing the impact of CD70 expression on the manufacture and functions of CAR-70 T-cells based on single-cell transcriptomics. Cancer Immunol Immunother. 2023; 72: 3163-3174.

[107]

Wagner K, Siska PJ. ‘living drugs’ target CD70 in advanced renal tumors. Trends Pharmacol Sci. 2024; 45: 757-759.

[108]

Cheng J, Ge T, Zhu X, et al. Preclinical development and evaluation of nanobody-based CD70-specific CAR T cells for the treatment of acute myeloid leukemia. Cancer Immunol Immunother. 2023; 72: 2331-2346.

[109]

Zhang B, Qin D, Mo Z, et al. Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors. Sci China Life Sci. 2016; 59: 340-348.

[110]

Zhang E, Gu J, Xu H. Prospects for chimeric antigen receptor-modified T cell therapy for solid tumors. Mol Cancer. 2018; 17: 7.

[111]

Rojas-Quintero J, Díaz MP, Palmar J, et al. Car T cells in solid tumors: overcoming obstacles. Int J Mol Sci. 2024; 25: 4170.

[112]

Jin L, Tao H, Karachi A, et al. CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors. Nat Commun. 2019; 10: 4016.

[113]

Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021; 11: 69.

[114]

Pan K, Farrukh H, Chittepu VCSR, Xu H, Pan C, Zhu Z. CAR race to cancer immunotherapy: from CAR T, CAR NK to CAR macrophage therapy. J Exp Clin Cancer Res. 2022; 41: 119.

[115]

Gong Y, Klein Wolterink RGJ, Wang J, Bos GMJ, Germeraad WTV. Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy. J Hematol OncolJ Hematol Oncol. 2021; 14: 73.

[116]

Dagher OK, Posey AD. Forks in the road for CAR T and CAR NK cell cancer therapies. Nat Immunol. 2023; 24: 1994-2007.

[117]

Ma S, Caligiuri MA, Yu J. Harnessing IL-15 signaling to potentiate NK cell-mediated cancer immunotherapy. Trends Immunol. 2022; 43: 833-847.

[118]

Van den Eynde A, Gehrcken L, Verhezen T, et al. IL-15-secreting CAR natural killer cells directed toward the pan-cancer target CD70 eliminate both cancer cells and cancer-associated fibroblasts. J Hematol OncolJ Hematol Oncol. 2024; 17: 8.

[119]

Wang L, Wang Y, He X, et al. CD70-targeted iPSC-derived CAR-NK cells display potent function against tumors and alloreactive T cells. Cell Rep Med. 2025; 6(1).

[120]

Acharya S, Basar R, Daher M, et al. CD28 costimulation augments CAR signaling in NK cells via the LCK/CD3ζ/ZAP70 signaling axis. Cancer Discov. 2024; 14: 1879-1900.

[121]

Peng L, Sferruzza G, Yang L, Zhou L, Chen S. CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors. Cell Mol Immunol. 2024; 21: 1089-1108.

[122]

Wang W, Liu Y, He Z, et al. Breakthrough of solid tumor treatment: cAR-NK immunotherapy. Cell Death Discov. 2024; 10: 40.

[123]

Li T, Niu M, Zhang W, Qin S, Zhou J, Yi M. CAR-NK cells for cancer immunotherapy: recent advances and future directions. Front Immunol. 2024; 15: 1361194.

[124]

Hegde PS, Chen DS. Top 10 challenges in cancer immunotherapy. Immunity. 2020; 52: 17-35.

[125]

Meric-Bernstam F, Larkin J, Tabernero J, Bonini C. Enhancing anti-tumour efficacy with immunotherapy combinations. Lancet Lond Engl. 2021; 397: 1010-1022.

[126]

Yan Y, Kumar AB, Finnes H, et al. Combining immune checkpoint inhibitors with conventional cancer therapy. Front Immunol. 2018; 9: 1739.

[127]

Fathi AT. Targeting CD70 in acute myeloid leukaemia: an emerging therapeutic angle in combinatorial treatment. Lancet Haematol. 2023; 10: e868-e870.

[128]

Marques-Piubelli ML, Kumar B, Basar R, et al. Increased expression of CD70 in relapsed acute myeloid leukemia after hypomethylating agents. Virchows Arch. 2024; 485: 937-941.

[129]

Riether C, Pabst T, Höpner S, et al. Targeting CD70 with cusatuzumab eliminates acute myeloid leukemia stem cells in patients treated with hypomethylating agents. Nat Med. 2020; 26: 1459-1467.

[130]

Pabst T, Vey N, Adès L, et al. Results from a phase I/II trial of cusatuzumab combined with azacitidine in patients with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy. Haematologica. 2023; 108: 1793-1802.

[131]

Pabst T, Papayannidis C, Demirkan F, et al. Cusatuzumab plus azacitidine in newly diagnosed acute myeloid leukaemia ineligible for intensive chemotherapy (CULMINATE): part one of a randomised, phase 2, dose optimisation study. Lancet Haematol. 2023; 10: e902-e912.

[132]

Ikezoe T, Usuki K, Aida K, Hatayama T, Shirahase T, Yamauchi T. Cusatuzumab plus azacitidine in japanese patients with newly diagnosed acute myeloid leukemia ineligible for intensive treatment. Cancer Sci. 2023; 114: 1037-1044.

[133]

Riether C, Schürch CM, Flury C, et al. Tyrosine kinase inhibitor-induced CD70 expression mediates drug resistance in leukemia stem cells by activating wnt signaling. Sci Transl Med. 2015; 7(298): 298ra119.

[134]

Flieswasser T, Van den Eynde A, Freire Boullosa L, et al. Targeting CD70 in combination with chemotherapy to enhance the anti-tumor immune effects in non-small cell lung cancer. OncoImmunology. 2023; 12: 2192100.

[135]

Mirazee J, Shah NN. CD70 CAR T cells in AML: form follows function. Cell Rep Med. 2022; 3: 100639.

[136]

Leick MB, Silva H, Scarfò I, et al. Non-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia. Cancer Cell. 2022; 40: 494-508.e5.

[137]

Rubino V, Hüppi M, Höpner S, et al. IL-21/IL-21R signaling renders acute myeloid leukemia stem cells more susceptible to cytarabine treatment and CAR T cell therapy. Cell Rep Med. 2024; 5: 101826.

[138]

Sedloev D, Chen Q, Unglaub JM, et al. Proteasome inhibition enhances the anti-leukemic efficacy of chimeric antigen receptor (CAR) expressing NK cells against acute myeloid leukemia. J Hematol Oncol J Hematol Oncol. 2024; 17: 85.

[139]

Ji F, Zhang F, Zhang M, et al. Targeting the DNA damage response enhances CD70 CAR-T cell therapy for renal carcinoma by activating the cGAS-STING pathway. J Hematol Oncol J Hematol Oncol. 2021; 14: 152.

[140]

Zhu G, Zhang J, Zhang Q, et al. Enhancement of CD70-specific CAR T treatment by IFN-γ released from oHSV-1-infected glioblastoma. Cancer Immunol Immunother. 2022; 71: 2433-2448.

[141]

Inaguma S, Ueki A, Lasota J, et al. cd70 and PD-L1 (CD274) co-expression predicts poor clinical outcomes in patients with pleural mesothelioma. J Pathol Clin Res. 2023; 9(3): 195-207.

[142]

Ning J, Hou X, Hao J, et al. METTL3 inhibition induced by M2 macrophage-derived extracellular vesicles drives anti-PD-1 therapy resistance via M6A-CD70-mediated immune suppression in thyroid cancer. Cell Death Differ. 2023; 30: 2265-2279.

[143]

Han BK, Olsen NJ, Bottaro A. The CD27-CD70 pathway and pathogenesis of autoimmune disease. Semin Arthritis Rheum. 2016; 45: 496-501.

[144]

Sperk M, Domselaar RV, Neogi U. Immune checkpoints as the immune system regulators and potential biomarkers in HIV-1 infection. Int J Mol Sci. 2018; 19: 2000.

[145]

Dhaeze T, Tremblay L, Lachance C, et al. CD70 defines a subset of proinflammatory and CNS-pathogenic TH1/TH17 lymphocytes and is overexpressed in multiple sclerosis. Cell Mol Immunol. 2019; 16: 652-665.

[146]

Liao W, Li M, Wu H, et al. Down-regulation of MBD4 contributes to hypomethylation and overexpression of CD70 in CD4+ T cells in systemic lupus erythematosus. Clin Epigenetics. 2017; 9: 104.

[147]

Sayed Mahmoud Marie RE, Abd El-Fadeel NM, El-Sayed Marei Y, Atef LM. Gene expression of CD70 and CD27 is increased in alopecia areata lesions and associated with disease severity and activity. Dermatol Res Pract. 2022; 2022: 5004642.

[148]

Wang X, Wei Y, He Z, et al. CD70-induced differentiation of proinflammatory Th1/17/22/GM lymphocytes associated with disease progression and immune reconstitution during HIV infection. Emerg Microbes Infect. 2023; 12: 2271068.

[149]

Pandey AK, Waldeck-Weiermair M, Wells QS, et al. Expression of CD70 modulates nitric oxide and redox status in endothelial cells. Arterioscler Thromb Vasc Biol. 2022; 42: 1169-1185.

[150]

Verma K, Croft W, Margielewska-Davies S, et al. CD70 identifies alloreactive T cells and represents a potential target for prevention and treatment of acute GVHD. Blood Adv. 2024; 8: 4900-4912.

[151]

Massicano AVF, Song PN, Mansur A, White SL, Sorace AG, Lapi SE. [89Zr]-atezolizumab-PET imaging reveals longitudinal alterations in PDL1 during therapy in TNBC preclinical models. Cancers. 2023; 15: 2708.

[152]

Vento J, Mulgaonkar A, Woolford L, et al. PD-L1 detection using 89Zr-atezolizumab immuno-PET in renal cell carcinoma tumorgrafts from a patient with favorable nivolumab response. J Immunother Cancer. 2019; 7: 144.

[153]

Bensch F, van der Veen EL, Lub-de Hooge MN, et al. 89Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer. Nat Med. 2018; 24: 1852-1858.

[154]

Wu Q, Shao H, Zhai W, et al. Molecular imaging of renal cell carcinomas: ready for prime time. Nat Rev Urol. 2024.

[155]

Suman SK, Subramanian S, Mukherjee A. Combination radionuclide therapy: a new paradigm. Nucl Med Biol. 2021; 98-99: 40-58.

[156]

Mahmoud AM, Nabavizadeh R, Rodrigues Pessoa R, et al. Antibody-based therapeutics for the treatment of renal cell carcinoma: challenges and opportunities. Oncologist. 2023; 28: 297-308.

[157]

Flugel CL, Majzner RG, Krenciute G, et al. Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours. Nat Rev Clin Oncol. 2023; 20: 49-62.

[158]

Liu C, Li J, Hu Q, Xu X, Zhang X. Generation of a CD70-specific fusion nanobody with IgG recruiting capacity for tumor killing. Int J Nanomedicine. 2023; 18: 3325-3338.

[159]

Bianchi M, Reichen C, Croset A, et al. The CD33xCD123xCD70 multispecific CD3-engaging DARPin MP0533 induces selective T cell-mediated killing of AML leukemic stem cells. Cancer Immunol Res. 2024; 12: 921-943.

[160]

Namdari H, Rezaei F, Heidarnejad F, Yaghoubzad-Maleki M, Karamigolbaghi M. Immunoinformatics approach to design a chimeric CD70-peptide vaccine against renal cell carcinoma. J Immunol Res. 2024; 2024: 1-25.

[161]

Adashek JJ, Munoz JL, Kurzrock R. If it is a solid tumor target, then it may be a hematologic cancer target: bridging the great divide. Med. 2024.

[162]

Komura M, Wang C, Ito S, et al., Simultaneous expression of CD70 and POSTN in cancer-associated fibroblasts predicts worse survival of colorectal cancer patients. Int J Mol Sci. 2024; 25: 2537.

[163]

Jacobs J, Deschoolmeester V, Zwaenepoel K, et al. Unveiling a CD70-positive subset of cancer-associated fibroblasts marked by pro-migratory activity and thriving regulatory T cell accumulation. OncoImmunology. 2018; 7: e1440167.

[164]

De Meulenaere A, Vermassen T, Aspeslagh S, et al. CD70 expression and its correlation with clinicopathological variables in squamous cell carcinoma of the head and neck. Pathobiology. 2016; 83(6): 327-333.

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2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.

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