Advances in CAR-T cell therapy for refractory diseases: challenges, innovations, clinical breakthroughs, and future prospects

Qibin Liao , Yunyu Mao , Meiqi Feng , Nairong Zheng , Xiangqing Ding , Xiaoyan Zhang , Zhongfang Wang , Jianqing Xu

Clinical Cancer Bulletin ›› 2025, Vol. 4 ›› Issue (1) : 21

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Clinical Cancer Bulletin ›› 2025, Vol. 4 ›› Issue (1) : 21 DOI: 10.1007/s44272-025-00050-2
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Advances in CAR-T cell therapy for refractory diseases: challenges, innovations, clinical breakthroughs, and future prospects

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Abstract

Chimeric antigen receptor-T (CAR-T) cell therapy has revolutionized cancer immunotherapy, enlightening new hope for patients with hematological malignancies and emerging potential in solid tumors and other refractory diseases. This review delves into the fundamentals, challenges, technological innovations, clinical breakthroughs, and future prospects of CAR-T cell therapy. It explores the mechanisms of action, evolution, key challenges such as toxicity and solid tumor resistance, recent technological advancements in CAR engineering, clinical breakthroughs in solid tumors and other refractory diseases, and future directions including next-generation constructs, gene editing, manufacturing scalability, and expansion beyond cancers. By synthesizing the latest research, this review aims to provide a comprehensive understanding of CAR-T cell therapy and its potential to transform cancer treatment and other therapeutic areas.

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CAR-T cell therapy / Challenges / Innovations / Clinical breakthroughs / Future prospects

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Qibin Liao, Yunyu Mao, Meiqi Feng, Nairong Zheng, Xiangqing Ding, Xiaoyan Zhang, Zhongfang Wang, Jianqing Xu. Advances in CAR-T cell therapy for refractory diseases: challenges, innovations, clinical breakthroughs, and future prospects. Clinical Cancer Bulletin, 2025, 4(1): 21 DOI:10.1007/s44272-025-00050-2

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References

[1]

June CH, O'Connor RS, Kawalekar OU. et al.. CAR T cell immunotherapy for human cancer. Science, 2018, 359(6382): 1361-1365.

[2]

Abbasi S, Totmaj MA, Abbasi M. et al.. Chimeric antigen receptor T (CAR-T) cells: novel cell therapy for hematological malignancies. Cancer Med, 2023, 12(7): 7844-7858.

[3]

Blüm P, Kayser S. Chimeric antigen receptor (CAR) T-cell therapy in hematologic malignancies: clinical implications and limitations. Cancers (Basel), 2024, 16(8. 1599

[4]

Ittershagen S, Ericson S, Eldjerou L. et al.. Industry's giant leap into cellular therapy: catalyzing chimeric antigen receptor T cell (CAR-T) immunotherapy. Curr Hematol Malig Rep, 2019, 14(1): 47-55.

[5]

Kiesgen S, Chicaybam L, Chintala NK. et al.. Chimeric antigen receptor (CAR) t-cell therapy for thoracic malignancies. J Thorac Oncol, 2018, 13(1): 16-26.

[6]

Thanindratarn P, Dean DC, Nelson SD. et al.. Chimeric antigen receptor T (CAR-T) cell immunotherapy for sarcomas: from mechanisms to potential clinical applications. Cancer Treat Rev, 2020, 82. 101934

[7]

Bonaldo G, Montanaro N, AlbertoVaccheri, et al. Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice. Eur J Clin Pharmacol. 2021;77(8):1225–1234.

[8]

Zhang C, Liu H. Advancements and Future Directions of Dual-Target Chimeric Antigen Receptor T-Cell Therapy in Preclinical and Clinical Studies. J Immunol Res, 2025, 2025: 5845167.

[9]

Wang Z, Chen C, Wang L. et al.. Chimeric antigen receptor T-cell therapy for multiple myeloma. Front Immunol, 2022, 13: 1050522.

[10]

Zhang PF, Xie D, Li Q. Chimeric antigen receptor T-cell therapy beyond cancer: current practice and future prospects. Immunotherapy, 2020, 12(13): 1021-1034.

[11]

Lee YH, Kim CH. Evolution of chimeric antigen receptor (CAR) T cell therapy: current status and future perspectives. Arch Pharm Res, 2019, 42(7): 607-616.

[12]

Xue F, Zheng P, Yang F. et al.. Salvage CD20-SD-CART therapy in aggressive B-cell lymphoma after CD19 CART treatment failure. Front Oncol, 2024, 14: 1376490.

[13]

Balagopalan L, Moreno T, Qin H. et al.. Generation of antitumor chimeric antigen receptors incorporating T cell signaling motifs. Sci Signal, 2024, 17(846. eadp8569

[14]

Beckers D, Jainarayanan AK, Dustin ML. et al.. T cell resistance: on the mechanisms of T cell non-activation. Immune Netw, 2024, 24(6. e42

[15]

Eshhar Z, Waks T, Gross G. et al.. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci U S A, 1993, 90(2): 720-724.

[16]

Chen AXY, Yap KM, Kim JS. et al.. Rewiring endogenous genes in CAR T cells for tumour-restricted payload delivery. Nature, 2025.

[17]

Labanieh L, Majzner RG, Klysz D. et al.. Enhanced safety and efficacy of protease-regulated CAR-T cell receptors. Cell, 2022, 185(10): 1745-1763.e22.

[18]

Nguyen HTX, Kim BG, Myers JT. et al.. Engineering TME-gated inducible CAR-T cell therapy for solid tumors. Mol Ther, 2025.

[19]

Shouval R, Strouse C, Kim S. et al.. Cytokine release syndrome and neurotoxicity following CD19 CAR-T in B-cell lymphoma. Transplant Cell Ther, 2025, 31(7): 419-433.

[20]

Renninger J, Kurz L, Stein H. Mitigation and management of common toxicities associated with the administration of CAR-T therapies in oncology patients. Drug Saf, 2025.

[21]

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, 2025, 26(1): 110-122.

[22]

Diorio C, Hernandez-Miyares L, Espinoza DA. et al.. Quadriparesis and paraparesis following chimeric antigen receptor T-cell therapy in children and adolescents. Blood, 2024, 144(13): 1387-1398.

[23]

Ma JF, Yan JW, Liu MJ. et al.. Safe and potent anti-CD19 CAR T-cells with shRNA-IL-6 gene silencing element in patients with refractory or relapsed B-cell acute lymphoblastic leukemia. Hemasphere, 2024, 8(10. e70007

[24]

Zhang P, Ying P, Li H. et al.. A novel safer CD19CAR with shrna interference of IFN-γ can reduce multiple cytokine levels without significantly compromising its killing efficacy. Apoptosis, 2024, 29(3–4): 556-567.

[25]

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(1): 49-62.

[26]

Yang Y, Vedvyas Y, Alcaina Y. et al.. Affinity-tuned mesothelin CAR T cells demonstrate enhanced targeting specificity and reduced off-tumor toxicity. JCI Insight, 2024, 9(22. e186268

[27]

Liao Q, Mao Y, He H. et al.. PD-L1 chimeric costimulatory receptor improves the efficacy of CAR-T cells for PD-L1-positive solid tumors and reduces toxicity in vivo. Biomark Res, 2020, 8(1): 57.

[28]

Choe JH, Watchmaker PB, Simic MS. et al.. Synnotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma. Sci Transl Med, 2021, 13(591. eabe7378

[29]

Dharani S, Cho H, Fernandez JP. et al.. TALEN-edited allogeneic inducible dual CAR T cells enable effective targeting of solid tumors while mitigating off-tumor toxicity. Mol Ther, 2024, 32(11): 3915-3931.

[30]

Jadlowsky JK, Hexner EO, Marshall A. et al.. Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies. Nat Med, 2025, 31(4): 1134-1144.

[31]

Dulery R, Guiraud V, Choquet S. et al.. T cell malignancies after CAR T cell therapy in the DESCAR-T registry. Nat Med, 2025, 31(4): 1130-1133.

[32]

Giordano Attianese GMP, Shui S, Cribioli E. et al.. Dual ON/OFF-switch chimeric antigen receptor controlled by two clinically approved drugs. Proc Natl Acad Sci U S A, 2024, 121(44. e2405085121

[33]

Cardle II, Scherer DR, Jensen MC. et al.. In situ bioconjugation of synthetic peptides onto universal chimeric antigen receptor T cells for targeted cancer immunotherapies. ACS Nano, 2025, 19(5): 5750-5768.

[34]

Liu L, He P, Wang Y. et al.. Engineering sonogenetic echoback-CAR T cells. Cell, 2025, 188(10): 2621-2636.e20.

[35]

Klabukov I, Kabakov AE, Yakimova A. et al.. Tumor-associated extracellular matrix obstacles for CAR-T cell therapy: approaches to overcoming. Curr Oncol, 2025, 32(2. 79

[36]

Hu MM, Zhao Y, Zhang N. et al.. Tumor microenvironment: obstacles and opportunities for T cell-based tumor immunotherapies. Mol Cancer Res, 2025, 23(4): 277-287.

[37]

Barish ME, Weng L, Awabdeh D. et al.. Spatial organization of heterogeneous immunotherapy target antigen expression in high-grade glioma. Neoplasia, 2022, 30. 100801

[38]

He D, Wang D, Lu P. et al.. Single-cell RNA sequencing reveals heterogeneous tumor and immune cell populations in early-stage lung adenocarcinomas harboring EGFR mutations. Oncogene, 2021, 40(2): 355-368.

[39]

Lu M, Zhang X, Gao X. et al.. Lenvatinib enhances T cell immunity and the efficacy of adoptive chimeric antigen receptor-modified T cells by decreasing myeloid-derived suppressor cells in cancer. Pharmacol Res, 2021, 174. 105829

[40]

Seo H, Chen J, González-Avalos E. et al.. TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8+ T cell exhaustion. Proc Natl Acad Sci U S A, 2019, 116(25): 12410-12415.

[41]

Zhang B, Liu J, Mo Y. et al.. CD8+ T cell exhaustion and its regulatory mechanisms in the tumor microenvironment: key to the success of immunotherapy. Front Immunol, 2024, 15: 1476904.

[42]

Zhu X, Hu H, Xiao Y. et al.. Tumor-derived extracellular vesicles induce invalid cytokine release and exhaustion of CD19 CAR-T cells. Cancer Lett, 2022, 536. 215668

[43]

Fu Y, Wang J, Liu C. et al.. Glycogen synthase kinase 3 controls T-cell exhaustion by regulating NFAT activation. Cell Mol Immunol, 2023, 20(10): 1127-1139.

[44]

Ledergor G, Fan Z, Wu K. et al.. CD4+ CAR t-cell exhaustion associated with early relapse of multiple myeloma after BCMA CAR t-cell therapy. Blood Adv, 2024, 8(13): 3562-3575.

[45]

Franco F, Jaccard A, Romero P. et al.. Metabolic and epigenetic regulation of T-cell exhaustion. Nat Metab, 2020, 2(10): 1001-1012.

[46]

Huang Y, Si X, Shao M. et al.. Rewiring mitochondrial metabolism to counteract exhaustion of CAR-T cells. J Hematol Oncol, 2022, 15(1): 38.

[47]

Bengsch B, Johnson AL, Kurachi M. et al.. Bioenergetic insufficiencies due to metabolic alterations regulated by the inhibitory receptor PD-1 are an early driver of CD8(+) T cell exhaustion. Immunity, 2016, 45(2): 358-373.

[48]

Lynn RC, Weber EW, Sotillo E. et al.. C-Jun overexpression in CAR T cells induces exhaustion resistance. Nature, 2019, 576(7786): 293-300.

[49]

Gao G, Liao W, Shu P. et al.. Targeting sphingosine 1-phosphate receptor 3 inhibits T-cell exhaustion and regulates recruitment of proinflammatory macrophages to improve antitumor efficacy of CAR-T cells against solid tumor. J Immunother Cancer, 2023, 11(8. e006343

[50]

Wang X, Tao X, Chen P. et al.. MEK inhibition prevents CAR-T cell exhaustion and differentiation via downregulation of c-Fos and JunB. Signal Transduct Target Ther, 2024, 9(1): 293.

[51]

Dan L, Kang-Zheng L. Optimizing viral transduction in immune cell therapy manufacturing: key process design considerations. J Transl Med, 2025, 23(1): 501.

[52]

Battiwalla M, Tees M, Flinn I. et al.. Access barriers to anti-CD19+ CART therapy for NHL across a community transplant and cellular therapy network. Blood Adv, 2025, 9(2): 429-435.

[53]

Diorio C, Teachey DT, Grupp SA. Allogeneic chimeric antigen receptor cell therapies for cancer: progress made and remaining roadblocks. Nat Rev Clin Oncol, 2025, 22(1): 10-27.

[54]

Wang J, Caimi PF. CAR assembly line: taking CAR T-cell manufacturing to the next level. Best Pract Res Clin Haematol, 2024, 37(4. 101595

[55]

Castellanos-Rueda R, Wang KK, Forster JL, et al. Dissecting the role of CAR signaling architectures on T cell activation and persistence using pooled screens and single-cell sequencing. Sci Adv. 2025;11(7):eadp4008.

[56]

Chen J, Qiu S, Li W. et al.. Tuning charge density of chimeric antigen receptor optimizes tonic signaling and CAR-T cell fitness. Cell Res, 2023, 33(5): 341-354.

[57]

Ebbinghaus M, Wittich K, Bancher B. et al.. Endogenous signaling molecule activating (ESMA) CARs: a novel CAR design showing a favorable risk to potency ratio for the treatment of triple negative breast cancer. Int J Mol Sci, 2024, 25(1. 615

[58]

Labanieh L, Mackall CL. CAR immune cells: design principles, resistance and the next generation. Nature, 2023, 614(7949): 635-648.

[59]

Chen W, Hong L, Lin S. et al.. Enhanced anti-tumor efficacy of "IL-15 and CCL19" -secreting CAR-T cells in human glioblastoma orthotopic xenograft model. Front Oncol, 2025, 15: 1539055.

[60]

Zhong W, Qin Z, Yu Z. et al.. Overcoming extracellular vesicle-mediated fratricide improves CAR T cell treatment against solid tumors. Nat Cancer, 2025, 6(7): 1157-1172.

[61]

Niu C, Wei H, Pan X. et al.. Foxp3 confers long-term efficacy of chimeric antigen receptor-T cells via metabolic reprogramming. Cell Metab, 2025, 37(6): 1426-1441.e7.

[62]

Pham-Danis C, Novak AJ, Danis E. et al.. Restoration of LAT activity improves CAR T cell sensitivity and persistence in response to antigen-low acute lymphoblastic leukemia. Cancer Cell, 2025, 43(3): 482-502.e9.

[63]

Xu X, Chen H, Ren Z. et al.. Phase separation of chimeric antigen receptor promotes immunological synapse maturation and persistent cytotoxicity. Immunity, 2024, 57(12): 2755-2771.e8.

[64]

Falgàs A, Lázaro-Gorines R, Zanetti SR. et al.. A TIM-3-Fc decoy secreted by engineered T cells improves CD19 CAR-T cell therapy in B-cell acute lymphoblastic leukemia. Blood, 2025.

[65]

Vogt KC, Silberman PC, Lin Q. et al.. Microenvironment actuated CAR T cells improve solid tumor efficacy without toxicity. Sci Adv, 2025, 11(4. eads3403

[66]

Wang Y, Han J, Wang D. et al.. Anti-PD-1 antibody armored γδ T cells enhance anti-tumor efficacy in ovarian cancer. Signal Transduct Target Ther, 2023, 8(1): 399.

[67]

Bubb QR, Balood M, Seir GE. et al.. Development of multivalent CAR T cells as dual immunotherapy and conditioning agents. Mol Ther Oncol, 2025, 33(1. 200944

[68]

Mao Y, Liao Q, Zhu Y. et al.. Efficacy and safety of novel multifunctional M10 CAR-T cells in HIV-1-infected patients: a phase I, multicenter, single-arm, open-label study. Cell Discov, 2024, 10(1): 49.

[69]

Li X, Chen T, Li X. et al.. Therapeutic targets of armored chimeric antigen receptor T cells navigating the tumor microenvironment. Exp Hematol Oncol, 2024, 13(1): 96.

[70]

Tipanee J, Samara-Kuko E, Gevaert T. et al.. Universal allogeneic CAR T cells engineered with sleeping beauty transposons and CRISPR-CAS9 for cancer immunotherapy. Mol Ther, 2022, 30(10): 3155-3175.

[71]

Hu Y, Zhou Y, Zhang M. et al.. CRISPR/Cas9-engineered universal CD19/CD22 dual-targeted CAR-T cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia. Clin Cancer Res, 2021, 27(10): 2764-2772.

[72]

Wang D, Wang X, Tan B, et al. Allogeneic CD19-targeted CAR-T therapy in refractory systemic lupus erythematosus achieved durable remission. Med. 2025:100749.

[73]

Zhang Y, Fang H, Wang G. et al.. Cyclosporine A-resistant CAR-T cells mediate antitumour immunity in the presence of allogeneic cells. Nat Commun, 2023, 14(1): 8491.

[74]

Zhu S, Zuo S, Li C. et al.. LLT1 overexpression renders allogeneic-NK resistance and facilitates the generation of enhanced universal CAR-T cells. J Exp Clin Cancer Res, 2025, 44(1): 25.

[75]

Mohammad A, Yurina A, Simonyan T. et al.. Modular (universal) CAR-T platforms in vivo: a comprehensive systematic review. Front Immunol, 2024, 15: 1409665.

[76]

Chen T, Deng J, Zhang Y. et al.. The construction of modular universal chimeric antigen receptor T (MU-CAR-T) cells by covalent linkage of allogeneic T cells and various antibody fragments. Mol Cancer, 2024, 23(1. 53

[77]

Dogan M, Karhan E, Kozhaya L. et al.. Engineering human MAIT cells with chimeric antigen receptors for cancer immunotherapy. J Immunol, 2022, 209(8): 1523-1531.

[78]

Coradin T, Keating AL, Barnard AR. et al.. Efficient in vivo generation of CAR T cells using a retargeted fourth-generation lentiviral vector. Mol Ther, 2025, S1525–0016(25): 00542-548

[79]

Xu J, Liu L, Parone P. et al.. In-vivo B-cell maturation antigen CAR T-cell therapy for relapsed or refractory multiple myeloma. Lancet, 2025, 406(10500): 228-231.

[80]

Bimbo JF, van Diest E, Murphy DE. et al.. T cell-specific non-viral DNA delivery and in vivo CAR-T generation using targeted lipid nanoparticles. J Immunother Cancer, 2025, 13(7. e011759

[81]

Hunter TL, Bao Y, Zhang Y. et al.. In vivo CAR T cell generation to treat cancer and autoimmune disease. Science, 2025, 388(6753): 1311-1317.

[82]

Rurik JG, Tombácz I, Yadegari A. et al.. CAR T cells produced in vivo to treat cardiac injury. Science, 2022, 375(6576): 91-96.

[83]

Bui TA, Mei H, Sang R. et al.. Advancements and challenges in developing in vivo CAR T cell therapies for cancer treatment. EBioMedicine, 2024, 106. 105266

[84]

Saiz LC, Leache L, Gutiérrez-Valencia M. et al.. Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies: a living systematic review on comparative studies. Ther Adv Hematol, 2023, 14. 20406207231168211

[85]

Laetsch TW, Maude SL, Rives S. et al.. Three-year update of Tisagenlecleucel in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia in the ELIANA trial. J Clin Oncol, 2023, 41(9): 1664-1669.

[86]

Jagannath S, Jackson CC, Schecter JM. et al.. Cilta-cel, a BCMA-targeting CAR-T therapy for patients with multiple myeloma. Expert Opin Biol Ther, 2024, 24(5): 339-350.

[87]

Du J, Qiang WT, Lu J. et al.. Updated results of a phase I open-label single-arm study of dual targeting BCMA and CD19 Fastcar-T cells (GC012F) as first-line therapy for transplant-eligible newly diagnosed high-risk multiple myeloma. Blood, 2023, 142(Supplement 1): 1022.

[88]

Svoboda J, Landsburg DJ, Gerson J. et al.. Enhanced CAR T-cell therapy for lymphoma after previous failure. N Engl J Med, 2025, 392(18): 1824-1835.

[89]

Hou B, Tang Y, Li W. et al.. Efficiency of CAR-T Therapy for Treatment of Solid Tumor in Clinical Trials: A Meta-Analysis. Dis Markers, 2019, 2019: 3425291.

[90]

Yu WL, Hua ZC. Chimeric antigen receptor T-cell (CAR T) therapy for hematologic and solid malignancies: efficacy and safety-a systematic review with meta-analysis. Cancers (Basel), 2019, 11(1. 47

[91]

Vitanza NA, Ronsley R, Choe M. et al.. Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial. Nat Med, 2025, 31(3): 861-868.

[92]

Pinto N, Albert CM, Taylor MR. et al.. STRIvE-02: A first-in-human phase I study of systemically administered B7–H3 chimeric antigen receptor T cells for patients with relapsed/refractory solid tumors. J Clin Oncol, 2024, 42(35): 4163-4172.

[93]

Qi C, Liu C, Gong J. et al.. Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial final results. Nat Med, 2024, 30(8): 2224-2234.

[94]

Qi C, Zhang P, Liu C. et al.. Safety and efficacy of CT041 in patients with refractory metastatic pancreatic cancer: a pooled analysis of two early-phase trials. J Clin Oncol, 2024, 42(21): 2565-2577.

[95]

Steffin D, Ghatwai N, Montalbano A. et al.. Interleukin-15-armoured GPC3 CAR T cells for patients with solid cancers. Nature, 2025, 637(8047): 940-946.

[96]

Pang N, Shi J, Qin L. et al.. IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin. J Hematol Oncol, 2021, 14(1): 118.

[97]

Shi D, Shi Y, Kaseb AO. 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): 3979-3989.

[98]

Chen N, Pu C, Zhao L. et al.. Chimeric antigen receptor T cells targeting CD19 and GCC in metastatic colorectal cancer: a nonrandomized clinical trial. JAMA Oncol, 2024, 10(11): 1532-1536.

[99]

Gargett T, Truong NTH, Gardam B. et al.. Safety and biological outcomes following a phase 1 trial of GD2-specific CAR-T cells in patients with GD2-positive metastatic melanoma and other solid cancers. J Immunother Cancer, 2024, 12(5. e008659

[100]

Quintarelli C, Del Bufalo F, De Ioris MA. et al.. Donor-derived GD2-specific CAR T cells in relapsed or refractory neuroblastoma. Nat Med, 2025, 31(3): 849-860.

[101]

Del Bufalo F, De Angelis B, Caruana I. et al.. GD2-CART01 for relapsed or refractory high-risk neuroblastoma. N Engl J Med, 2023, 388(14): 1284-1295.

[102]

Pal SK, Tran B, Haanen JBAG. et al.. CD70-targeted allogeneic CAR T-cell therapy for advanced clear cell renal cell carcinoma. Cancer Discov, 2024, 14(7): 1176-1189.

[103]

Mackensen A, Haanen JBAG, Koenecke C. et al.. CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial. Nat Med, 2023, 29(11): 2844-2853.

[104]

Shah PD, Huang AC, Xu X. et al.. Phase I trial of autologous RNA-electroporated cMET-directed CAR T cells administered intravenously in patients with melanoma and breast carcinoma. Cancer Res Commun, 2023, 3(5): 821-829.

[105]

Narayan V, Barber-Rotenberg JS, Jung IY. 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): 724-734.

[106]

Zeng L, Li Y, Xiang W. et al.. Advances in chimeric antigen receptor T cell therapy for autoimmune and autoinflammatory diseases and their complications. J Autoimmun, 2025, 150. 103350

[107]

Caël B, Bôle-Richard E, Garnache Ottou F. et al.. Chimeric antigen receptor-modified T-cell therapy: recent updates and challenges in autoimmune diseases. J Allergy Clin Immunol, 2025, 155(3): 688-700.

[108]

Mougiakakos D, Krönke G, Völkl S. et al.. CD19-targeted CAR t cells in refractory systemic lupus erythematosus. N Engl J Med, 2021, 385(6): 567-569.

[109]

Müller F, Taubmann J, Bucci L. et al.. CD19 CAR t-cell therapy in autoimmune disease - a case series with follow-up. N Engl J Med, 2024, 390(8): 687-700.

[110]

Li M, Zhang Y, Jiang N. et al.. Anti-CD19 CAR T cells in refractory immune thrombocytopenia of SLE. N Engl J Med, 2024, 391(4): 376-378.

[111]

Wang X, Wu X, Tan B. et al.. Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis. Cell, 2024, 187(18): 4890-4904.e9.

[112]

Neurology Society of China Alliance for Rare Diseases, Chinese Myasthenia Gravis Collaboration Group of China Alliance for Rare Diseases, Chinese Society of Neuromuscular Disease, et al. Expert consensus on chimeric antigen receptor T cell therapy for neurological autoimmune diseases in China 2025. Chin J Neurol. 2025; 58(4): 347–358. https://doi.org/10.3760/cma.j.cn113694-20250115-00035.

[113]

Wu L, Zhu L, Chen J. Diverse potential of chimeric antigen receptor-engineered cell therapy: beyond cancer. Clin Transl Med, 2025, 15(4. e70306

[114]

Seif M, Einsele H, Löffler J. CAR T cells beyond cancer: hope for immunomodulatory therapy of infectious diseases. Front Immunol, 2019, 10: 2711.

[115]

Liu B, Zhang W, Xia B. et al.. Broadly neutralizing antibody-derived CAR T cells reduce viral reservoir in individuals infected with HIV-1. J Clin Invest, 2021, 131(19. e150211

[116]

Meng L, Zhao H, Chang S, et al. Engineering of CD8+ T cells with an HIV-specific synthetic notch receptor to secrete broadly therapeutic antibodies for combining antiviral humoral and cellular immune responses. mBio. 2025;16(4):e0383924..

[117]

Yashaswini CN, Cogliati B, Qin T, et al. In vivo anti-FAP CAR T therapy reduces fibrosis and restores liver homeostasis in metabolic dysfunction-associated steatohepatitis. bioRxiv [Preprint]. 2025:2025.02.25.640143.

[118]

Amor C, Fernández-Maestre I, Chowdhury S. et al.. Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction. Nat Aging, 2024, 4(3): 336-349.

[119]

Patel KK, Tariveranmoshabad M, Kadu S. et al.. From concept to cure: the evolution of CAR-T cell therapy. Mol Ther, 2025, 33(5): 2123-2140.

[120]

Guo Q, Huang L, Liu Y. et al.. PcoCas12a: a novel CRISPR enzyme from Prevotella copri enhancing TCR-T-cell tumor suppression. Int J Biol Macromol, 2025, 298. 139740

[121]

Nakagawara K, Ando M, Srirat T. et al.. NR4A ablation improves mitochondrial fitness for long persistence in human CAR-T cells against solid tumors. J Immunother Cancer, 2024, 12(8. e008665

[122]

Agarwal S, Aznar MA, Rech AJ. et al.. Deletion of the inhibitory co-receptor CTLA-4 enhances and invigorates chimeric antigen receptor T cells. Immunity, 2023, 56(10): 2388-2407.e9.

[123]

Giuffrida L, Sek K, Henderson MA. et al.. CRISPR/Cas9 mediated deletion of the adenosine A2A receptor enhances CAR T cell efficacy. Nat Commun, 2021, 12(1): 3236.

[124]

Adusumilli PS, Zauderer MG, Rivière I. 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): 2748-2763.

[125]

Miklos DB, Riedell PA, Bokun A. et al.. Leveraging the immunomodulatory potential of Ibrutinib for improved outcomes of T cell-mediated therapies of B cell malignancies: a narrative review. Target Oncol, 2025, 20(2): 217-234.

[126]

Abdalsalam NMF, Ibrahim A, Saliu MA. et al.. MDSC: a new potential breakthrough in CAR-T therapy for solid tumors. Cell Commun Signal, 2024, 22(1): 612.

[127]

Ponterio E, Haas TL, De Maria R. Oncolytic virus and CAR-T cell therapy in solid tumors. Front Immunol, 2024, 15: 1455163.

[128]

Zhu T, Xiao Y, Chen Z. et al.. Inhalable nanovesicles loaded with a STING agonist enhance CAR-T cell activity against solid tumors in the lung. Nat Commun, 2025, 16(1): 262.

[129]

Ghassemi S, Durgin JS, Nunez-Cruz S. et al.. Rapid manufacturing of non-activated potent CAR T cells. Nat Biomed Eng, 2022, 6(2): 118-128.

[130]

Gehrke L, Gonçalves VDR, Andrae D. et al.. Current non-viral-based strategies to manufacture CAR-T cells. Int J Mol Sci, 2024, 25(24. 13685

[131]

Hu X, White K, Olroyd AG. et al.. Hypoimmune CD19 CAR T cells treat allogeneic mice with features of spontaneous systemic lupus erythematosus. iScience, 2025, 28(7. 112806

[132]

Huang Y, Wang H. Tonic signaling in CAR-T therapy: the lever long enough to move the planet. Front Med, 2025.

Funding

Key Technologies Research and Development Program(2024YFC2311100)

Innovative Research Group Project of the National Natural Science Foundation of China(82402147)

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