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Target selection and clinical chimeric antigen receptor T cell activity against solid tumors
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Chimeric antigen receptor (CAR) T cell therapy is a relatively new form of targeted therapy that has demonstrated impressive success in treating hematological malignancies. It has been challenging to translate this success to solid tumors. Reasons for this include barriers to delivery, tumor heterogeneity, cancer cells' ability to evade the immune system as well as identifying the optimal target. Most CAR T clinical trials have targeted well‐characterized cancer targets with significant preclinical and in some cases clinical validation. Published results from some of these trials show signs of anti‐cancer activity that warrant encouragement, but also caution, given instances of unacceptable toxicity. The narrow therapeutic window is complicated by the ability of CAR T cells to expand in patients regardless of dose. Here, we review those trials showing encouraging results in the context of target selection. It is clear that more specific tumor targeting is required, either by affinity tuning to avoid low‐level target expression in healthy cells, logic gating, or the identification of new targets that are more cancer specific.
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Target selection and clinical chimeric antigen receptor T cell activity against solid tumors
(
),
Abstract
Chimeric antigen receptor (CAR) T cell therapy is a relatively new form of targeted therapy that has demonstrated impressive success in treating hematological malignancies. It has been challenging to translate this success to solid tumors. Reasons for this include barriers to delivery, tumor heterogeneity, cancer cells' ability to evade the immune system as well as identifying the optimal target. Most CAR T clinical trials have targeted well‐characterized cancer targets with significant preclinical and in some cases clinical validation. Published results from some of these trials show signs of anti‐cancer activity that warrant encouragement, but also caution, given instances of unacceptable toxicity. The narrow therapeutic window is complicated by the ability of CAR T cells to expand in patients regardless of dose. Here, we review those trials showing encouraging results in the context of target selection. It is clear that more specific tumor targeting is required, either by affinity tuning to avoid low‐level target expression in healthy cells, logic gating, or the identification of new targets that are more cancer specific.
References(87)
MacKay M, Afshinnekoo E, Rub J, Hassan C, Khunte M, Baskaran N, et al. The therapeutic landscape for cells engineered with chimeric antigen receptors. Nat Biotechnol. 2020;38(2): 233–44. https://doi.org/10.1038/s41587‐019‐0329‐2
Monsivais D, Vasquez YM, Chen F, Zhang Y, Chandrashekar DS, Faver JC, et al. Mass‐spectrometry‐based proteomic correlates of grade and stage reveal pathways and kinases associated with aggressive human cancers. Oncogene. 2021;40(11): 2081–95. https://doi.org/10.1038/s41388‐021‐01681‐0
Allen GM, Lim WA. Rethinking cancer targeting strategies in the era of smart cell therapeutics. Nat Rev Cancer. 2022;22(12): 693–702. https://doi.org/10.1038/s41568‐022‐00505‐x
Chakradhar S. Driving CARs: as ‘living drugs’, T cell therapies face dose standardization woes. Nat Med. 2015;21(11): 1236–8. https://www.nature.com/articles/nm1115‐1236
O’Donnell JS, Teng MWL, Smyth MJ. Cancer immunoediting and resistance to T cell‐based immunotherapy. Nat Rev Clin Oncol. 2019;16(3): 151–67. https://doi.org/10.1038/s41571‐018‐0142‐8
Cheever MA, Allison JP, Ferris AS, Finn OJ, Hastings BM, Hecht TT, et al. The prioritization of cancer antigens: a national cancer institute pilot project for the acceleration of translational research. Clin Cancer Res. 2009;15(17): 5323–37. https://doi.org/10.1158/1078‐0432.ccr‐09‐0737
Wang SS, Luong K, Gracey FM, Jabar S, McColl B, Cross RS, et al. A novel peptide‐MHC targeted chimeric antigen receptor T cell forms a T cell‐like immune synapse. Biomedicines. 2021;9(12): 1875. https://doi.org/10.3390/biomedicines9121875
Ordóñez NG. Application of mesothelin immunostaining in tumor diagnosis. Am J Surg Pathol. 2003;27(11): 1418–28. https://doi.org/10.1097/00000478‐200311000‐00003
Haas AR, Tanyi JL, O’Hara MH, Gladney WL, Lacey SF, Torigian DA, et al. Phase Ⅰ study of lentiviral‐transduced chimeric antigen receptor‐modified T cells recognizing mesothelin in advanced solid cancers. Mol Ther. 2019;27(11): 1919–29. https://www.sciencedirect.com/science/article/pii/S1525001619303284
Adusumilli PS, Zauderer MG, Rivière I, Solomon SB, Rusch VW, O’Cearbhaill RE, et al. A phase Ⅰ trial of regional mesothelin‐targeted CAR T‐cell therapy in patients with malignant pleural disease, in combination with the anti‐PD‐1 agent pembrolizumab. Cancer Discov. 2021;11(11): 2748–63. https://doi.org/10.1158/2159‐8290.cd‐21‐0407
Tanyi J, Haas A, Aggarwal C, O’Hara M, Lacey S, Golden R, et al. Phase Ⅰ study of autologous T cells bearing fully‐humanized chimeric antigen receptors targeting mesothelin in mesothelin‐expressing cancers (314). Gynecol Oncol [Internet]. 2022;166: S164–5. https://www.sciencedirect.com/science/article/pii/S0090825822015372
Louis CU, Savoldo B, Dotti G, Pule M, Yvon E, Myers GD, et al. Antitumor activity and long‐term fate of chimeric antigen receptor‐positive T cells in patients with neuroblastoma. Blood. 2011;118(23): 6050–6. https://doi.org/10.1182/blood‐2011‐05‐354449
Heczey A, Louis CU, Savoldo B, Dakhova O, Durett A, Grilley B, et al. CAR T cells administered in combination with lymphodepletion and PD‐1 inhibition to patients with neuroblastoma. Mol Ther. 2017;25(9): 2214–24. https://doi.org/10.1016/j.ymthe.2017.05.012
Straathof K, Flutter B, Wallace R, Jain N, Loka T, Depani S, et al. Antitumor activity without on‐target off‐tumor toxicity of GD2‐chimeric antigen receptor T cells in patients with neuroblastoma. Sci Transl Med. 2020;12(571): eabd6169. https://doi.org/10.1126/scitranslmed.abd6169
Yu L, Huang L, Lin D, Lai X, Wu L, Liao X, et al. GD2‐specific chimeric antigen receptor‐modified T cells for the treatment of refractory and/or recurrent neuroblastoma in pediatric patients. J Cancer Res Clin Oncol. 2022;148(10): 2643–52. https://doi.org/10.1007/s00432‐021‐03839‐5
Majzner RG, Ramakrishna S, Yeom KW, Patel S, Chinnasamy H, Schultz LM, et al. GD2‐CAR T cell therapy for H3K27M‐mutated diffuse midline gliomas. Nature. 2022;603(7903): 934–41. https://doi.org/10.1038/s41586‐022‐04489‐4
Shi D, Shi Y, Kaseb AO, Qi X, Zhang Y, Chi J, et al. Chimeric antigen receptor‐glypican‐3 T‐cell therapy for advanced hepatocellular carcinoma: results of phase Ⅰ trials. Clin Cancer Res. 2020;26(15): 3979–89. https://doi.org/10.1158/1078‐0432.ccr‐19‐3259
Fang W, Fu Q, Zhao Q, Zheng Y, Liu L, Li Z, et al. Phase Ⅰ trial of fourth‐generation chimeric antigen receptor T‐cells targeting glypican‐3 for advanced hepatocellular carcinoma. JCO [Internet]. 2021;39(15_suppl): 4088. https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.4088
Sun H, Xing C, Jiang S, Yu K, Dai S, Kong H, et al. Long term complete response of advanced hepatocellular carcinoma to glypican‐3 specific chimeric antigen receptor T‐Cells plus sorafenib, a case report. Front Immunol. 2022;13: 963031. https://doi.org/10.3389/fimmu.2022.963031
Zhao Z, Guo W, Fang S, Song S, Song J, Teng F, et al. An armored GPC3‐directed CAR‐T for refractory or relapsed hepatocellular carcinoma in China: A phase Ⅰ trial. JCO [Internet]. 2021;39(15_suppl): 4095. https://ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.4095
Zhang C, Wang Z, Yang Z, Wang M, Li S, Li Y, et al. Phase Ⅰ escalating‐dose trial of CAR‐T therapy targeting CEA+ metastatic colorectal cancers. Mol Ther. 2017;25(5): 1248–58. https://doi.org/10.1016/j.ymthe.2017.03.010
Katz SC, Moody AE, Guha P, Hardaway JC, Prince E, LaPorte J, et al. HITM‐SURE: hepatic immunotherapy for metastases phase Ib anti‐CEA CAR‐T study utilizing pressure enabled drug delivery. J Immunother Cancer. 2020;8(2): e001097. https://doi.org/10.1136/jitc‐2020‐001097
Hegde M, DeRenzo CC, Zhang H, Mata M, Gerken C, Shree A, et al. Expansion of HER2‐CAR T cells after lymphodepletion and clinical responses in patients with advanced sarcoma. JCO [Internet]. 2017;35(15_suppl): 10508. https://ascopubs.org/doi/10.1200/JCO.2017.35.15_suppl.10508
Ahmed N, Brawley V, Hegde M, Bielamowicz K, Kalra M, Landi D, et al. HER2‐Specific chimeric antigen receptor‐modified virus‐specific T cells for progressive glioblastoma: a phase 1 dose‐escalation trial. JAMA Oncol. 2017;3(8): 1094–101. https://doi.org/10.1001/jamaoncol.2017.0184
Zhan X, Wang B, Li Z, Li J, Wang H, Chen L, et al. Phase Ⅰ trial of Claudin 18.2‐specific chimeric antigen receptor T cells for advanced gastric and pancreatic adenocarcinoma. JCO [Internet]. 2019;37(15_suppl):2509. https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.2509
Qi C, Gong J, Li J, Liu D, Qin Y, Ge S, et al. Claudin18.2‐specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results. Nat Med. 2022;28(6):1189–98. https://www.nature.com/articles/s41591‐022‐01800‐8
Haanen JB, Mackensen A, Koenecke C, Alsdorf W, Wagner‐Drouet E, Heudobler D, et al. Abstract CT002: BNT211: a Phase Ⅰ trial to evaluate safety and efficacy of CLDN6 CAR‐T cells and CARVac‐mediated in vivo expansion in patients with CLDN6‐positive advanced solid tumors. Cancer Res. 2022;82(12_Supplement):CT002. https://doi.org/10.1158/1538‐7445.AM2022‐CT002
Lin Y, Chen S, Zhong S, An H, Yin H, McGowan E. Phase Ⅰ clinical trial of PD‐1 knockout anti‐MUC1 CAR‐T cells in the treatment of patients with non‐small cell lung cancer. Ann Oncol. 2019;30:xi12. https://www.annalsofoncology.org/article/S0923‐7534(20)34414‐8/fulltext
Li Q, Wang Y, Lin M, Xia L, Bao Y, Sun X, et al. Abstract A014: phase Ⅰ clinical trial with PD‐1/MUC1 CAR‐pNK92 immunotherapy. Cancer Immunol Res. 2019;7(2_Supplement):A014. https://doi.org/10.1158/2326‐6074.CRICIMTEATIAACR18‐A014
Junghans RP, Ma Q, Rathore R, Gomes EM, Bais AJ, Lo ASY, et al. Phase Ⅰ trial of anti‐PSMA designer CAR‐T cells in prostate cancer: possible role for interacting interleukin 2‐T cell pharmacodynamics as a determinant of clinical response. Prostate. 2016;76(14):1257–70. https://doi.org/10.1002/pros.23214
Narayan V, Barber‐Rotenberg JS, Jung IY, Lacey SF, Rech AJ, Davis MM, et al. PSMA‐targeting TGFβ‐insensitive armored CAR T cells in metastatic castration‐resistant prostate cancer: a phase 1 trial. Nat Med. 2022;28(4):724–34. https://doi.org/10.1038/s41591‐022‐01726‐1
Slovin SF, Dorff TB, Falchook GS, Wei XX, Gao X, McKay RR, et al. Phase 1 study of P‐PSMA‐101 CAR‐T cells in patients with metastatic castration‐resistant prostate cancer (mCRPC). JCO. 2022;40(6_suppl):98. https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.6_suppl.098
Bharadwaj U, Li M, Chen C, Yao Q. Mesothelin‐induced pancreatic cancer cell proliferation involves alteration of cyclin E via activation of signal transducer and activator of transcription protein 3. Mol Cancer Res. 2008;6(11):1755–65. https://doi.org/10.1158/1541‐7786.mcr‐08‐0095
Greenbaum U, Yalniz FF, Srour SA, Rezvani K, Singh H, Olson A, et al. Chimeric antigen receptor therapy: how are we driving in solid tumors? Biol Blood Marrow Transplant. 2020;26(10):1759–69. https://doi.org/10.1016/j.bbmt.2020.06.020
Castelletti L, Yeo D, van Zandwijk N, Rasko JEJ. Anti‐Mesothelin CAR T cell therapy for malignant mesothelioma. Biomarker Res. 2021;9(1):11. https://doi.org/10.1186/s40364‐021‐00264‐1
Beatty GL, O’Hara MH, Lacey SF, Torigian DA, Nazimuddin F, Chen F, et al. Activity of mesothelin‐specific chimeric antigen receptor T cells against pancreatic carcinoma metastases in a phase 1 trial. Gastroenterology. 2018;155(1):29–32. https://doi.org/10.1053/j.gastro.2018.03.029
Nazha B, Inal C, Owonikoko TK. Disialoganglioside GD2 expression in solid tumors and role as a target for cancer therapy. Front Oncol. 2020;10:1000. https://doi.org/10.3389/fonc.2020.01000
Richman SA, Nunez‐Cruz S, Moghimi B, Li LZ, Gershenson ZT, Mourelatos Z, et al. High‐affinity GD2‐specific CAR T cells induce fatal encephalitis in a preclinical neuroblastoma model. Cancer Immunol Res. 2018;6(1):36–46. https://doi.org/10.1158/2326‐6066.CIR‐17‐0211
Lammie G, Cheung N, Gerald W, Rosenblum M, Cordoncardo C. Ganglioside GD(2) expression in the human nervous‐system and in neuroblastomas – an immunohistochemical study. Int J Oncol. 1993;3(5):909–15. https://doi.org/10.3892/ijo.3.5.909
Zheng X, Liu X, Lei Y, Wang G, Liu M. Glypican‐3: a novel and promising target for the treatment of hepatocellular carcinoma. Front Oncol. 2022;12:824208. https://doi.org/10.3389/fonc.2022.824208
Baumhoer D, Tornillo L, Stadlmann S, Roncalli M, Diamantis EK, Terracciano LM. Glypican 3 expression in human nonneoplastic, preneoplastic, and neoplastic tissues: a tissue microarray analysis of 4,387 tissue samples. Am J Clin Pathol. 2008;129(6):899–906. https://doi.org/10.1309/hcqwpwd50xhd2dw6
Liu X, Onda M, Watson N, Hassan R, Ho M, Bera TK, et al. Highly active CAR T cells that bind to a juxtamembrane region of mesothelin and are not blocked by shed mesothelin. Proc Natl Acad Sci U S A. 2022;119(19):e2202439119. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171807/
Hall C, Clarke L, Pal A, Buchwald P, Eglinton T, Wakeman C, et al. A review of the role of carcinoembryonic antigen in clinical practice. Ann Coloproctol. 2019;35(6):294–305. https://doi.org/10.3393/ac.2019.11.13
Patel U, Abernathy J, Savani BN, Oluwole O, Sengsayadeth S, Dholaria B. CAR T cell therapy in solid tumors: a review of current clinical trials. EJHaem. 2022;3(Suppl 1):24–31. https://doi.org/10.1002/jha2.356
Wu S, Gu W. Association of T Stage and serum CEA levels in determining survival of rectal cancer. Front Med. 2019;6:270. https://doi.org/10.3389/fmed.2019.00270
Lee JH, Lee SW. The roles of carcinoembryonic antigen in liver metastasis and therapeutic approaches. Gastroenterol Res Pract. 2017;2017:7521987. https://doi.org/10.1155/2017/7521987
Thistlethwaite FC, Gilham DE, Guest RD, Rothwell DG, Pillai M, Burt DJ, et al. The clinical efficacy of first‐generation carcinoembryonic antigen (CEACAM5)‐specific CAR T cells is limited by poor persistence and transient pre‐conditioning‐dependent respiratory toxicity. Cancer Immunol Immunother. 2017;66(11):1425–36. https://doi.org/10.1007/s00262‐017‐2034‐7
Adamczyk A, Grela‐Wojewoda A, Domagała‐Haduch M, Ambicka A, Harazin‐Lechowska A, Janecka A, et al. Proteins involved in HER2 signalling pathway, their relations and influence on metastasis‐free survival in HER2‐positive breast cancer patients treated with Trastuzumab in adjuvant setting. J Cancer. 2017;8(1):131–9. https://doi.org/10.7150/jca.16239
Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther. 2010;18(4):843–51. https://doi.org/10.1038/mt.2010.24
Ahmed N, Brawley VS, Hegde M, Robertson C, Ghazi A, Gerken C, et al. Human epidermal growth factor receptor 2 (HER2) – specific chimeric antigen receptor–modified T cells for the immunotherapy of HER2‐positive sarcoma. JCO. 2015;33(15):1688–96. https://ascopubs.org/doi/full/10.1200/JCO.2014.58.0225
Hegde M, Joseph SK, Pashankar F, DeRenzo C, Sanber K, Navai S, et al. Tumor response and endogenous immune reactivity after administration of HER2 CAR T cells in a child with metastatic rhabdomyosarcoma. Nat Commun. 2020;11(1):3549. https://doi.org/10.1038/s41467‐020‐17175‐8
Arnold A, Daum S, von Winterfeld M, Berg E, Hummel M, Rau B, et al. Prognostic impact of Claudin 18.2 in gastric and esophageal adenocarcinomas. Clin Transl Oncol. 2020;22(12):2357–63. https://doi.org/10.1007/s12094‐020‐02380‐0
Kyuno D, Takasawa A, Takasawa K, Ono Y, Aoyama T, Magara K, et al. Claudin‐18.2 as a therapeutic target in cancers: cumulative findings from basic research and clinical trials. Tissue Barriers. 2022;10(1):1967080. https://doi.org/10.1080/21688370.2021.1967080
Xu X, Jin H, Liu Y, Liu L, Wu Q, Guo Y, et al. The expression patterns and correlations of claudin‐6, methy‐CpG binding protein 2, DNA methyltransferase 1, histone deacetylase 1, acetyl‐histone H3 and acetyl‐histone H4 and their clinicopathological significance in breast invasive ductal carcinomas. Diagn Pathol. 2012;7(1):33. https://doi.org/10.1186/1746‐1596‐7‐33
Stadler CR, Bähr‐Mahmud H, Plum LM, Schmoldt K, Kölsch AC, Türeci Ö, et al. Characterization of the first‐in‐class T‐cell‐engaging bispecific single‐chain antibody for targeted immunotherapy of solid tumors expressing the oncofetal protein claudin 6. OncoImmunology. 2016;5(3):e1091555. https://doi.org/10.1080/2162402x.2015.1091555
Reinhard K, Rengstl B, Oehm P, Michel K, Billmeier A, Hayduk N, et al. An RNA vaccine drives expansion and efficacy of claudin‐CAR‐T cells against solid tumors. Science. 2020;367(6476):446–53. https://doi.org/10.1126/science.aay5967
Taylor‐Papadimitriou J, Burchell JM, Graham R, Beatson R. Latest developments in MUC1 immunotherapy. Biochem Soc Trans. 2018;46(3):659–68. https://doi.org/10.1042/BST20170400
Bose M, Mukherjee P. Potential of anti‐MUC1 antibodies as a targeted therapy for gastrointestinal cancers. Vaccines (Basel). 2020;8(4):659. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712407/
Saeland E, Belo AI, Mongera S, van Die I, Meijer GA, van Kooyk Y. Differential glycosylation of MUC1 and CEACAM5 between normal mucosa and tumour tissue of colon cancer patients. Int J Cancer. 2012;131(1):117–28. https://doi.org/10.1002/ijc.26354
Horm TM, Schroeder JA. MUC1 and metastatic cancer: expression, function and therapeutic targeting. Cell Adh Migr. 2013;7(2):187–98. https://doi.org/10.4161/cam.23131
Ghosh SK, Pantazopoulos P, Medarova Z, Moore A. Expression of underglycosylated MUC1 antigen in cancerous and adjacent normal breast tissues. Clin Breast Cancer. 2013;13(2):109–18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578066/
Caromile LA, Shapiro LH. PSMA redirects MAPK to PI3K‐AKT signaling to promote prostate cancer progression. Mol Cell Oncol. 2017;4(4):e1321168. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5540209/
Gladney W, Vultur A, Schweizer M, Fraietta J, Rech A, June C, et al. 335 Analyses of severe immune‐mediated toxicity in patients with advanced mCRPC treated with a PSMA‐targeted armored CAR T‐cells. J Immunother Cancer. 2022;10(Suppl 2). https://jitc.bmj.com/content/10/Suppl_2/A353
Barros LRC, Couto SCF, da Silva Santurio D, Paixão EA, Cardoso F, da Silva VJ, et al. Systematic review of available CAR‐T cell trials around the world. Cancers. 2022;14(11):2667. https://doi.org/10.3390/cancers14112667
Barrett D, Chagin K, Fountaine TJ, Moore A, Ka M, Gladney W, et al. TmPSMA‐02: a CD2 endodomain containing double armored PSMA CAR T with enhanced efficacy and lower immune toxicity. JCO. 2022;40(6_suppl):158. https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.6_suppl.158
Morris EC, Neelapu SS, Giavridis T, Sadelain M. Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nat Rev Immunol. 2022;22(2):85–96. https://www.nature.com/articles/s41577‐021‐00547‐6
Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, et al. Chimeric antigen receptor T‐cell therapy — assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15(1):47–62. https://www.nature.com/articles/nrclinonc.2017.148
Lamers CH, Sleijfer S, van Steenbergen S, van Elzakker P, van Krimpen B, Groot C, et al. Treatment of metastatic renal cell carcinoma with CAIX CAR‐engineered T cells: clinical evaluation and management of on‐target toxicity. Mol Ther. 2013;21(4):904–12. https://doi.org/10.1038/mt.2013.17
Silver DA, Pellicer I, Fair WR, Heston WD, Cordon‐Cardo C. Prostate‐specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 1997;3(1):81–5.
Bonini C, Ferrari G, Verzeletti S, Servida P, Zappone E, Ruggieri L, et al. HSV‐TK gene transfer into donor lymphocytes for control of allogeneic graft‐versus‐leukemia. Science. 1997;276(5319):1719–24. https://doi.org/10.1126/science.276.5319.1719
Kalinin RS, Petukhov AV, Knorre VD, Maschan MA, Stepanov AV, Gabibov AG. Molecular approaches to safe and controlled engineered T‐cell therapy. Acta Naturae. 2018;10(2):16–23. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6087824/
Caruso HG, Hurton LV, Najjar A, Rushworth D, Ang S, Olivares S, et al. Tuning sensitivity of CAR to EGFR density limits recognition of normal tissue while maintaining potent antitumor activity. Cancer Res. 2015;75(17):3505–18. https://doi.org/10.1158/0008‐5472.CAN‐15‐0139
Liu X, Jiang S, Fang C, Yang S, Olalere D, Pequignot EC, et al. Affinity‐tuned ErbB2 or EGFR chimeric antigen receptor T cells exhibit an increased therapeutic index against tumors in mice. Cancer Res. 2015;75(17):3596–607. https://doi.org/10.1158/0008‐5472.CAN‐15‐0159
Park S, Shevlin E, Vedvyas Y, Zaman M, Park S, Hsu YMS, et al. Micromolar affinity CAR T cells to ICAM‐1 achieves rapid tumor elimination while avoiding systemic toxicity. Sci Rep. 2017;7(1):14366. https://doi.org/10.1038/s41598‐017‐14749‐3
Vander Mause ER, Atanackovic D, Lim CS, Luetkens T. Roadmap to affinity‐tuned antibodies for enhanced chimeric antigen receptor T cell function and selectivity. Trends Biotechnol. 2022;40(7):875–90. https://www.sciencedirect.com/science/article/pii/S0167779921003152
Mansilla‐Soto J, Eyquem J, Haubner S, Hamieh M, Feucht J, Paillon N, et al. HLA‐independent T cell receptors for targeting tumors with low antigen density. Nat Med. 2022;28(2):345–52. https://doi.org/10.1038/s41591‐021‐01621‐1
You Y, Lai X, Pan Y, Zheng H, Vera J, Liu S, et al. Artificial intelligence in cancer target identification and drug discovery. Signal Transduct Target Ther. 2022;7(1):156. https://doi.org/10.1038/s41392‐022‐00994‐0
Rose M, Cardon T, Aboulouard S, Hajjaji N, Kobeissy F, Duhamel M, et al. Surfaceome proteomic of glioblastoma revealed potential targets for immunotherapy. Front Immunol. 2021;12:746168. https://doi.org/10.3389/fimmu.2021.746168
Lee JK, Bangayan NJ, Chai T, Smith BA, Pariva TE, Yun S, et al. Systemic surfaceome profiling identifies target antigens for immune‐based therapy in subtypes of advanced prostate cancer. Proc Natl Acad Sci U S A. 2018;115(19):E4473–82. https://doi.org/10.1073/pnas.1802354115
Bogetofte Barnkob M, Vitting‐Seerup K, Rønn Olsen L. Target isoforms are an overlooked challenge and opportunity in chimeric antigen receptor cell therapy. Immunother Adv. 2022;2(1):ltac009. https://doi.org/10.1093/immadv/ltac009
Raglow Z, McKenna MK, Bonifant CL, Wang W, Pasca di Magliano M, Stadlmann J, et al. Targeting glycans for CAR therapy: the advent of sweet CARs. Mol Ther. 2022;30(9):2881–90. https://www.sciencedirect.com/science/article/pii/S1525001622004270
O’Rourke DM, Nasrallah MP, Desai A, Melenhorst JJ, Mansfield K, Morrissette JJD, et al. A single dose of peripherally infused EGFRvIII‐directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med. 2017;9(399):eaaa0984. https://www.science.org/doi/full/10.1126/scitranslmed.aaa0984
Mao R, Kong W, He Y. The affinity of antigen‐binding domain on the antitumor efficacy of CAR T cells: moderate is better. Front Immunol. 2022;13:1032403. https://doi.org/10.3389/fimmu.2022.1032403
Karam A, Mjaess G, Martinez Chanza N, Aoun F, Bou Kheir G, Younes H, et al. CAR‐T cell therapy for solid tumors: are we still that far? A systematic review of literature. Cancer Invest. 2022;40(10):923–37. https://doi.org/10.1080/07357907.2022.2125004
Mehrabadi AZ, Ranjbar R, Farzanehpour M, Shahriary A, Dorostkar R, Hamidinejad MA, et al. Therapeutic potential of CAR T cell in malignancies: a scoping review. Biomed Pharmacother. 2022;146:112512. https://doi.org/10.1016/j.biopha.2021.112512
Abbott RC, Hughes‐Parry HE, Jenkins MR. To go or not to go? Biological logic gating engineered T cells. J Immunother Cancer. 2022;10(4):e004185. https://jitc.bmj.com/lookup/doi/10.1136/jitc‐2021‐004185
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