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Recent Advances and Challenges in Cancer Treatment with Car T Cell Therapy: A Novel Anti-cancer Strategy

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Abstract

Over the past decade, there has been continuous advancement in immunotherapy to improve human health. A promising technique that has emerged is chimeric antigen receptor (CAR)-T cell therapy, which presents an innovative approach to treating cancer. While CAR-T technology has shown success in treating blood cancers, it encounters challenges in addressing solid tumors. These challenges encompass the absence of dependable tumor-associated antigens, tumor heterogeneity, immunosuppressive tumor environments, and reduced T cell infiltration. To address these challenges, current research is focused on identifying dependable tumor-associated antigens and creating cost-effective, tumor microenvironment-specific CAR-T cells. These efforts aim to enhance the efficacy of CAR-T cell therapy for solid tumors. This review provides an overview of the development of CAR-T therapy for different types of tumors, encompassing both solid and hematological tumors. It outlines the challenges encountered in CAR-T cell therapy and proposes Approaches to address these obstacles.

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References

  1. June, C. H., et al. (2018). CAR T cell immunotherapy for human cancer. Science, 359(6382), 1361–1365.

    Article  Google Scholar 

  2. June, C. H., & Sadelain, M. (2018). Chimeric antigen receptor therapy. New England Journal of Medicine, 379(1), 64–73.

    Article  Google Scholar 

  3. Sadelain, M., Rivière, I., & Riddell, S. (2017). Therapeutic T cell engineering. Nature, 545(7655), 423–431.

    Article  Google Scholar 

  4. Sadelain, M., Brentjens, R., & Rivière, I. (2013). The basic principles of chimeric antigen receptor design. Cancer Discovery, 3(4), 388–398.

    Article  Google Scholar 

  5. Kochenderfer, J. N., et al. (2012). B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor–transduced T cells. Blood, The Journal of the American Society of Hematology, 119(12), 2709–2720.

    Google Scholar 

  6. Akbari, H., Mousazadeh, H., Akbarzadeh, A., et al. (2022). Co-loading of cisplatin and methotrexate in nanoparticle-based PCL-PEG system enhances lung cancer chemotherapy effects. Journal of Cluster Science, 33, 1751–1762.

    Article  Google Scholar 

  7. Neelapu, S. S., et al. (2017). Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. New England Journal of Medicine, 377(26), 2531–2544.

    Article  Google Scholar 

  8. Abramson, J. S., et al. (2020). Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. The Lancet, 396(10254), 839–852.

    Article  Google Scholar 

  9. Martin, T., et al. (2023). Ciltacabtagene autoleucel, an anti–B-cell maturation antigen chimeric antigen receptor T-cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE-1 2-year follow-up. Journal of Clinical Oncology, 41(6), 1265.

    Article  Google Scholar 

  10. Munshi, N. C., et al. (2021). Idecabtagene vicleucel in relapsed and refractory multiple myeloma. New England Journal of Medicine, 384(8), 705–716.

    Article  Google Scholar 

  11. Lin, Y.-J., Mashouf, L. A., & Lim, M. (2022). CAR T cell therapy in primary brain tumors: Current investigations and the future. Frontiers in Immunology, 13, 817296.

    Article  Google Scholar 

  12. Rafiq, S., Hackett, C. S., & Brentjens, R. J. (2020). Engineering strategies to overcome the current roadblocks in CAR T cell therapy. Nature reviews Clinical Oncology, 17(3), 147–167.

    Article  Google Scholar 

  13. Newick, K., et al. (2017). CAR T cell therapy for solid tumors. Annual review of Medicine, 68, 139–152.

    Article  Google Scholar 

  14. Keshavarz, A., et al. (2022). Recent findings on chimeric antigen receptor (CAR)-engineered immune cell therapy in solid tumors and hematological malignancies. Stem Cell Research & Therapy, 13(1), 1–22.

    Article  Google Scholar 

  15. Patel, U., et al. (2022). CAR T cell therapy in solid tumors: A review of current clinical trials. EJHaem, 3, 24–31.

    Article  Google Scholar 

  16. Chandran, S. S., & Klebanoff, C. A. (2019). T cell receptor-based cancer immunotherapy: Emerging efficacy and pathways of resistance. Immunological Reviews, 290(1), 127–147.

    Article  Google Scholar 

  17. Zhang, C., et al. (2017). Engineering car-t cells. Biomarker Research, 5(1), 1–6.

    Article  Google Scholar 

  18. Lam, N., et al. (2020). Anti-BCMA chimeric antigen receptors with fully human heavy-chain-only antigen recognition domains. Nature Communications, 11(1), 283.

    Article  Google Scholar 

  19. Nakajima, M., et al. (2019). Improved survival of chimeric antigen receptor-engineered T (CAR-T) and tumor-specific T cells caused by anti-programmed cell death protein 1 single-chain variable fragment-producing CAR-T cells. Cancer Science, 110(10), 3079–3088.

    Article  Google Scholar 

  20. Alabanza, L., et al. (2017). Function of novel anti-CD19 chimeric antigen receptors with human variable regions is affected by hinge and transmembrane domains. Molecular Therapy, 25(11), 2452–2465.

    Article  Google Scholar 

  21. Stornaiuolo, A., et al. (2021). Characterization and functional analysis of CD44v6. CAR T cells endowed with a new low-affinity nerve growth factor receptor-based spacer. Human Gene Therapy, 32(13–14), 744–760.

    Article  Google Scholar 

  22. Morales, L., & Paramio, J. M. (2021). Cell therapies in bladder cancer management. International Journal of Molecular Sciences, 22(6), 2818.

    Article  Google Scholar 

  23. Julamanee, J., et al. (2021). Composite CD79A/CD40 co-stimulatory endodomain enhances CD19CAR-T cell proliferation and survival. Molecular Therapy, 29(9), 2677–2690.

    Article  Google Scholar 

  24. Dotti, G., et al. (2014). Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunological Reviews, 257(1), 107–126.

    Article  Google Scholar 

  25. Sterner, R. C., & Sterner, R. M. (2021). CAR-T cell therapy: Current limitations and potential strategies. Blood Cancer Journal, 11(4), 69.

    Article  MathSciNet  Google Scholar 

  26. Muller, Y. D., et al. (2021). The CD28-transmembrane domain mediates chimeric antigen receptor heterodimerization with CD28. Frontiers in Immunology, 12, 500.

    Article  Google Scholar 

  27. Lanitis, E., Coukos, G., & Irving, M. (2020). All systems go: Converging synthetic biology and combinatorial treatment for CAR-T cell therapy. Current Opinion in Biotechnology, 65, 75–87.

    Article  Google Scholar 

  28. Janeway, C. A. Jr, Travers, P., Walport, M., & Shlomchik, M. J. (2001). Antigen receptor structure and signaling pathways. In Immunobiology: The immune system in health and disease (5th ed.). Garland Science.

  29. Hamieh, M., et al. (2023). Programming CAR T cell tumor recognition: Tuned antigen sensing and logic gating. Cancer Discovery, 13(4), 829–843.

    Article  Google Scholar 

  30. Yan, T., Zhu, L., & Chen, J. (2023). Current advances and challenges in CAR T-Cell therapy for solid tumors: Tumor-associated antigens and the tumor microenvironment. Experimental Hematology & Oncology, 12(1), 14.

    Article  Google Scholar 

  31. Brentjens, R. J., & Curran, K. J. (2012). Novel cellular therapies for leukemia: CAR-modified T cells targeted to the CD19 antigen. Hematology 2010, the American Society of Hematology Education Program Book, 1, 143–151.

  32. Hiltensperger, M., & Krackhardt, A. M. (2023). Current and future concepts for the generation and application of genetically engineered CAR-T and TCR-T cells. Frontiers in Immunology, 14, 1121030.

    Article  Google Scholar 

  33. Abbasi, S., Totmaj, M. A., Abbasi, M., Hajazimian, S., Goleij, P., Behroozi, J., Shademan, B., Isazadeh, A., & Baradaran, B. (2023). Chimeric antigen receptor T (CAR-T) cells: Novel cell therapy for hematological malignancies. Cancer Medicine, 12(7), 7844–7858.

    Article  Google Scholar 

  34. Chmielewski, M., & Abken, H. (2015). TRUCKs: The fourth generation of CARs. Expert Opinion On Biological Therapy, 15(8), 1145–1154.

    Article  Google Scholar 

  35. Parikh, R. H., & Lonial, S. (2023). Chimeric antigen receptor T-cell therapy in multiple myeloma: A comprehensive review of current data and implications for clinical practice. CA: A Cancer Journal for Clinicians, 73(3), 275–285.

    Google Scholar 

  36. Subklewe, M., von Bergwelt-Baildon, M., & Humpe, A. (2019). Chimeric antigen receptor T cells: A race to revolutionize cancer therapy. Transfusion Medicine and Hemotherapy, 46(1), 15–24.

    Article  Google Scholar 

  37. Schepisi, G., et al. (2023). The new frontier of immunotherapy: Chimeric antigen receptor T (CAR-T) cell and macrophage (CAR-M) therapy against breast cancer. Cancers, 15(5), 1597.

    Article  Google Scholar 

  38. Jan, M., et al. (2021). Reversible ON-and OFF-switch chimeric antigen receptors controlled by lenalidomide. Science Translational Medicine, 13(575), eabb6295.

    Article  Google Scholar 

  39. Mellatyar, H., Talaei, S., & Nejati-Koshki, K. (2016). Targeting HSP90 gene expression with 17-DMAG nanoparticles in breast cancer cells. Asian Pacific Journal of Cancer Prevention, 17(5), 2453–2457.

    Google Scholar 

  40. Panahi, Y., Mohammadhosseini, M., Abadi, A. J., Akbarzadeh, A., & Mellatyar, H. (2016). An update on biomedical application of nanotechnology for Alzheimer’s disease diagnosis and therapy. Drug Research, 66(11), 580–586.

  41. Norelli, M., et al. (2018). Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells. Nature medicine, 24(6), 739–748.

    Article  Google Scholar 

  42. Shimabukuro-Vornhagen, A., et al. (2018). Cytokine release syndrome. Journal for Immunotherapy of Cancer, 6(1), 1–14.

    Article  Google Scholar 

  43. Santomasso, B., et al. (2019). The other side of CAR T-cell therapy: Cytokine release syndrome, neurologic toxicity, and financial burden. American Society of Clinical Oncology Educational Book, 39, 433–444.

    Article  Google Scholar 

  44. Smith, L. T. (2017). Cytokine release syndrome: inpatient care for side effects of CAR T-cell therapy. Clinical Journal of Oncology Nursing, 21(2), 29–34.

    Article  Google Scholar 

  45. Maude, S. L., et al. (2014). Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer Journal (Sudbury, Mass.), 20(2), 119.

    Article  Google Scholar 

  46. Neelapu, S. S., et al. (2018). Toxicity management after chimeric antigen receptor T cell therapy: One size does not fit’ALL’. Nature Reviews Clinical Oncology, 15(4), 218–218.

    Article  Google Scholar 

  47. Riegler, L. L., Jones, G. P., & Lee, D. W. (2019). Current approaches in the grading and management of cytokine release syndrome after chimeric antigen receptor T-cell therapy. Therapeutics and Clinical Risk Management, 15, 323–335.

    Article  Google Scholar 

  48. Neelapu, S. S., et al. (2018). Chimeric antigen receptor T-cell therapy—Assessment and management of toxicities. Nature Reviews Clinical Oncology, 15(1), 47–62.

    Article  Google Scholar 

  49. Locke, F. L., et al. (2017). Preliminary results of prophylactic tocilizumab after axicabtageneciloleucel (axi-cel; KTE-C19) treatment for patients with refractory, aggressive non-Hodgkin lymphoma (NHL). Blood, 130, 1547.

    Article  Google Scholar 

  50. Topp, M., et al. (2019). Earlier steroid use with axicabtagene ciloleucel (Axi-Cel) in patients with relapsed/refractory large B cell lymphoma. Blood, 134, 243.

    Article  Google Scholar 

  51. Khan, A. N., et al. (2024). CAR-T cell therapy in hematological malignancies: Where are we now and where are we heading for? European Journal of Haematology, 112(1), 6–18.

    Article  Google Scholar 

  52. Majzner, R. G., et al. (2020). Tuning the antigen density requirement for CAR T-cell activity. Cancer discovery, 10(5), 702–723.

    Article  Google Scholar 

  53. Ramello, M. C., et al. (2019). An immunoproteomic approach to characterize the CAR interactome and signalosome. Science Signaling, 12(568), eaap9777.

    Article  Google Scholar 

  54. Di Stasi, A., et al. (2011). Inducible apoptosis as a safety switch for adoptive cell therapy. New England Journal of Medicine, 365(18), 1673–1683.

    Article  Google Scholar 

  55. Diaconu, I., et al. (2017). Inducible caspase-9 selectively modulates the toxicities of CD19-specific chimeric antigen receptor-modified T cells. Molecular Therapy, 25(3), 580–592.

    Article  Google Scholar 

  56. Santiago-Vicente, Y., de Jesús Castillejos-López, M., Carmona-Aparicio, L., Coballase-Urrutia, E., Velasco-Hidalgo, L., Niembro-Zúñiga, A. M., Zapata-Tarrés, M., & Torres-Espíndola, L. M. (2024). Immunotherapy for pediatric gliomas: CAR-T cells against B7H3: A review of the literature. CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders), 23(4), 420–430.

  57. Juillerat, A., et al. (2019). Modulation of chimeric antigen receptor surface expression by a small molecule switch. BMC biotechnology, 19, 1–9.

    Article  Google Scholar 

  58. Gauthier, J., et al. (2020). Feasibility and efficacy of CD19-targeted CAR T cells with concurrent ibrutinib for CLL after ibrutinib failure. Blood, The Journal of the American Society of Hematology, 135(19), 1650–1660.

    Google Scholar 

  59. Yu, H., et al. (2017). Repeated loss of target surface antigen after immunotherapy in primary mediastinal large B cell lymphoma. American Journal of Hematology, 92(1), E11.

    Article  Google Scholar 

  60. Taubmann, J., et al. (2024). Rescue therapy of antisynthetase syndrome with CD19-targeted CAR-T cells after failure of several B-cell depleting antibodies. Rheumatology, 63(1), e12–e14.

    Article  Google Scholar 

  61. Hamieh, M., et al. (2019). CAR T cell trogocytosis and cooperative killing regulate tumour antigen escape. Nature, 568(7750), 112–116.

    Article  Google Scholar 

  62. Jackson, H. J., & Brentjens, R. J. (2015). Overcoming antigen escape with CAR T-cell therapy. Cancer Discovery, 5(12), 1238–1240.

    Article  Google Scholar 

  63. Okada, M., Shimizu, K., & Fujii, S.-I. (2022). Identification of neoantigens in cancer cells as targets for immunotherapy. International Journal of Molecular Sciences, 23(5), 2594.

    Article  Google Scholar 

  64. Hegde, M., et al. (2013). Combinational targeting offsets antigen escape and enhances effector functions of adoptively transferred T cells in glioblastoma. Molecular Therapy, 21(11), 2087–2101.

    Article  Google Scholar 

  65. Zah, E., et al. (2016). T cells expressing CD19/CD20 bispecific chimeric antigen receptors prevent antigen escape by malignant B cells. Cancer Immunology Research, 4(6), 498–508.

    Article  Google Scholar 

  66. Qin, H., et al. (2018). Preclinical development of bivalent chimeric antigen receptors targeting both CD19 and CD22. Molecular Therapy-Oncolytics, 11, 127–137.

    Article  Google Scholar 

  67. Pan, J., et al. (2020). Sequential CD19-22 CAR T therapy induces sustained remission in children with r/r B-ALL. Blood, The Journal of the American Society of Hematology, 135(5), 387–391.

    Google Scholar 

  68. Goebeler, M.-E., & Bargou, R. C. (2020). T cell-engaging therapies—BiTEs and beyond. Nature Reviews Clinical Oncology, 17(7), 418–434.

    Article  Google Scholar 

  69. Jen, E. Y., et al. (2019). FDA approval: Blinatumomab for patients with B-cell precursor acute lymphoblastic leukemia in morphologic remission with minimal residual disease. Clinical Cancer Research, 25(2), 473–477.

    Article  Google Scholar 

  70. Borogovac, A., & Siddiqi, T. (2024). Transforming CLL management with immunotherapy: Investigating the potential of CAR T-cells and bispecific antibodies. In Seminars in hematology. WB Saunders.

  71. Zhai, Y., Hong, J., Wang, J., Jiang, Y., Wu, W., Lv, Y., Guo, J., Tian, L., Sun, H., Li, Y., & Li, C. (2024). Comparison of blinatumomab and CAR T-cell therapy in relapsed/refractory acute lymphoblastic leukemia: A systematic review and meta-analysis. Expert Review of Hematology, 17(1–3), 67–76.

    Article  Google Scholar 

  72. Subklewe, M. (2021). BiTEs better than CAR T cells. Blood Advances, 5(2), 607–612.

    Article  Google Scholar 

  73. Chen, Y.-J., Abila, B., & Mostafa Kamel, Y. (2023). CAR-T: What is next? Cancers, 15(3), 663.

    Article  Google Scholar 

  74. Choi, B. D., et al. (2019). CAR-T cells secreting BiTEs circumvent antigen escape without detectable toxicity. Nature Biotechnology, 37(9), 1049–1058.

    Article  Google Scholar 

  75. Yang, J., et al. (2023). BCMA-targeting chimeric antigen receptor T-cell therapy for multiple myeloma. Cancer Letters, 553, 215949.

    Article  Google Scholar 

  76. Krenciute, G., et al. (2016). 76. Transgenic expression of IL15 improves antiglioma activity of IL13Rα2-CAR T cells. Molecular Therapy, 24, S33.

    Article  Google Scholar 

  77. Krenciute, G., et al. (2017). Transgenic expression of IL15 improves antiglioma activity of IL13Rα2-CAR T cells but results in antigen loss variants. Cancer Immunology Research, 5(7), 571–581.

    Article  Google Scholar 

  78. Zarrabi, K. K., et al. (2023). Bispecific PSMA antibodies and CAR-T in metastatic castration-resistant prostate cancer. Therapeutic Advances in Urology, 15, 17562872231182220.

    Article  Google Scholar 

  79. Liu, X., Zhang, N., & Shi, H. (2017). Driving better and safer HER2-specific CARs for cancer therapy. Oncotarget, 8(37), 62730.

    Article  Google Scholar 

  80. Cappell, K. M., & Kochenderfer, J. N. (2023). Long-term outcomes following CAR T cell therapy: What we know so far. Nature Reviews Clinical Oncology, 20(6), 359–371.

    Article  Google Scholar 

  81. Yang, J., et al. (2023). Advancing CAR T cell therapy through the use of multidimensional omics data. Nature Reviews Clinical Oncology, 20(4), 211–228.

    Article  Google Scholar 

  82. Bhat, A. A., et al. (2021). Cytokine-chemokine network driven metastasis in esophageal cancer; promising avenue for targeted therapy. Molecular Cancer, 20(1), 1–20.

    Article  Google Scholar 

  83. Nisar, S., et al. (2021). Chemokine-cytokine networks in the head and neck tumor microenvironment. International Journal of Molecular Sciences, 22(9), 4584.

    Article  Google Scholar 

  84. Ager, A. (2017). High endothelial venules and other blood vessels: Critical regulators of lymphoid organ development and function. Frontiers in Immunology, 8, 45.

    Article  Google Scholar 

  85. Yang, J., Yan, J., & Liu, B. (2018). Targeting VEGF/VEGFR to modulate antitumor immunity. Frontiers in Immunology, 9, 978.

    Article  Google Scholar 

  86. Zhang, P., Zhang, G., & Wan, X. (2023). Challenges and new technologies in adoptive cell therapy. Journal of Hematology & Oncology, 16(1), 97.

    Article  Google Scholar 

  87. Zhang, B.-L., et al. (2016). Hurdles of CAR-T cell-based cancer immunotherapy directed against solid tumors. Science China Life Sciences, 59, 340–348.

    Article  Google Scholar 

  88. Caruana, I., et al. (2015). Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes. Nature Medicine, 21(5), 524–529.

    Article  Google Scholar 

  89. Can, C. A. R. T. C., & Growth, I. T. (2014). Targeting fibroblast activation protein in tumor stroma with. Cancer, 2(2), 154.

    Google Scholar 

  90. Moon, E. K., et al. (2018). Intra-tumoral delivery of CXCL11 via a vaccinia virus, but not by modified T cells, enhances the efficacy of adoptive T cell therapy and vaccines. Oncoimmunology, 7(3), e1395997.

    Article  Google Scholar 

  91. Adachi, K., et al. (2018). IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor. Nature Biotechnology, 36(4), 346–351.

    Article  Google Scholar 

  92. Tchou, J., et al. (2017). Safety and efficacy of intratumoral injections of chimeric antigen receptor (CAR) T cells in metastatic breast cancer. Cancer Immunology Research, 5(12), 1152–1161.

    Article  Google Scholar 

  93. Nellan, A., et al. (2018). Durable regression of medulloblastoma after regional and intravenous delivery of anti-HER2 chimeric antigen receptor T cells. Journal for Immunotherapy of Cancer, 6(1), 1–14.

    Article  Google Scholar 

  94. Klampatsa, A., et al. (2017). Intracavitary ‘T4 immunotherapy’of malignant mesothelioma using pan-ErbB re-targeted CAR T-cells. Cancer Letters, 393, 52–59.

    Article  Google Scholar 

  95. Katz, S., et al. (2016). Regional CAR-T cell infusions for peritoneal carcinomatosis are superior to systemic delivery. Cancer Gene Therapy, 23(5), 142–148.

    Article  Google Scholar 

  96. Zhu, W. M., & Middleton, M. R. (2023). Combination therapies for the optimisation of bispecific T-cell engagers in cancer treatment. Immunotherapy Advances, 3(1), ltad013.

    Article  Google Scholar 

  97. ElSamadisy, O., et al. (2024). Safe, efficient, and comfortable reinforcement-learning-based car-following for AVs with an analytic safety guarantee and dynamic target speed. Transportation Research Record, 2678(1), 643–661.

    Article  Google Scholar 

  98. Fisher, J., et al. (2017). Avoidance of on-target off-tumor activation using a co-stimulation-only chimeric antigen receptor. Molecular Therapy, 25(5), 1234–1247.

    Article  Google Scholar 

  99. Schneider, M., et al. (2015). CD38 is expressed on inflammatory cells of the intestine and promotes intestinal inflammation. PLoS ONE, 10(5), e0126007.

    Article  Google Scholar 

  100. Mizuguchi, M., et al. (1995). Neuronal localization of CD38 antigen in the human brain. Brain Research, 697(1–2), 235–240.

    Article  Google Scholar 

  101. Dwivedi, S., Rendón-Huerta, E. P., Ortiz-Navarrete, V., & Montaño, L. F. (2021). CD38 and regulation of the immune response cells in cancer. Journal of Oncology, 2021, 6630295.

  102. Steentoft, C., et al. (2018). Glycan-directed CAR-T cells. Glycobiology, 28(9), 656–669.

    Article  Google Scholar 

  103. Pinto, S. N., & Krenciute, G. (2024). The mechanisms of altered blood–brain barrier permeability in CD19 CAR T–cell recipients. International Journal of Molecular Sciences, 25(1), 644.

    Article  Google Scholar 

  104. Suarez, E. R., et al. (2016). Chimeric antigen receptor T cells secreting anti-PD-L1 antibodies more effectively regress renal cell carcinoma in a humanized mouse model. Oncotarget, 7(23), 34341.

    Article  Google Scholar 

  105. Zhu, X., et al. (2017). CAR-T cell therapy in ovarian cancer: From the bench to the bedside. Oncotarget, 8(38), 64607.

    Article  Google Scholar 

  106. Morgan, R. A., et al. (2010). Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Molecular Therapy, 18(4), 843–851.

    Article  Google Scholar 

  107. Daei Sorkhabi, A., et al. (2023). The current landscape of CAR T-cell therapy for solid tumors: Mechanisms, research progress, challenges, and counterstrategies. Frontiers in Immunology, 14, 1113882.

    Article  Google Scholar 

  108. Moradi, V., Omidkhoda, A., & Ahmadbeigi, N. (2023). The paths and challenges of “off-the-shelf” CAR-T cell therapy: An overview of clinical trials. Biomedicine & Pharmacotherapy, 169, 115888.

    Article  Google Scholar 

  109. Kringel, R., Lamszus, K., & Mohme, M. (2023). Chimeric antigen receptor T cells in glioblastoma—Current concepts and promising future. Cells, 12(13), 1770.

    Article  Google Scholar 

  110. Park, S., et al. (2017). Micromolar affinity CAR T cells to ICAM-1 achieves rapid tumor elimination while avoiding systemic toxicity. Scientific Reports, 7(1), 14366.

    Article  Google Scholar 

  111. Oluwole, O. O., et al. (2021). Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma. British Journal of Haematology, 194(4), 690–700.

    Article  Google Scholar 

  112. Fry, T. J., et al. (2018). CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nature Medicine, 24(1), 20–28.

    Article  Google Scholar 

  113. Fry, T. J., et al. (2018). CD22-CAR T cells induce remissions in CD19-CAR naïve and resistant B-ALL. Nature Medicine, 24(1), 20.

    Article  Google Scholar 

  114. Jia, Q., et al. (2022). Heterogeneity of the tumor immune microenvironment and its clinical relevance. Experimental Hematology & Oncology, 11(1), 24.

    Article  MathSciNet  Google Scholar 

  115. Liu, G., et al. (2021). Enhancing CAR-T cell efficacy in solid tumors by targeting the tumor microenvironment. Cellular & Molecular Immunology, 18(5), 1085–1095.

    Article  Google Scholar 

  116. Lin, H.-W., Liu, J.-Y., & Luo, W.-X. (2023). Advances in CAR-T combination therapy for solid tumors. China Biotechnology, 42(12), 37–51.

    Google Scholar 

  117. Obiorah, I., & Courville, E. L. (2023). Diagnostic flow cytometry in the era of targeted therapies: Lessons from therapeutic monoclonal antibodies and chimeric antigen receptor T-cell adoptive immunotherapy. Surgical Pathology Clinics, 16(2), 423–431.

    Article  Google Scholar 

  118. Holstein, S. A., Grant, S. J., & Wildes, T. M. (2023). Chimeric antigen receptor T-cell and bispecific antibody therapy in multiple myeloma: Moving into the future. Journal of Clinical Oncology, 41(27), 4416–4429.

    Article  Google Scholar 

  119. Aparicio, C., et al. (2021). Cell therapy for colorectal cancer: The promise of chimeric antigen receptor (CAR)-T cells. International Journal of Molecular Sciences, 22(21), 11781.

    Article  Google Scholar 

  120. Pearlman, A. H., et al. (2021). Targeting public neoantigens for cancer immunotherapy. Nature Cancer, 2(5), 487–497.

    Article  Google Scholar 

  121. Lang, F., et al. (2022). Identification of neoantigens for individualized therapeutic cancer vaccines. Nature reviews Drug discovery, 21(4), 261–282.

    Article  Google Scholar 

  122. Marques-Piubelli, M. L., Kim, D. H., Medeiros, L. J., Lu, W., Khan, K., Gomez-Bolanos, L. I., Rodriguez, S., Parra, E. R., Ok, C. Y., Aradhya, A., & Solis, L. M. (2023). CD30 expression is frequently decreased in relapsed classic Hodgkin lymphoma after anti-CD30 CAR T-cell therapy. Histopathology, 83(1), 143–148.

    Article  Google Scholar 

  123. Blass, E., & Ott, P. A. (2021). Advances in the development of personalized neoantigen-based therapeutic cancer vaccines. Nature Reviews Clinical Oncology, 18(4), 215–229.

    Article  Google Scholar 

  124. Zhang, Q., et al. (2022). Neoantigens in precision cancer immunotherapy: From identification to clinical applications. Chinese Medical Journal, 135(11), 1285–1298.

    Article  Google Scholar 

  125. Gao, J., et al. (2021). Complete rejection of large established breast cancer by local immunochemotherapy with T cell activation against neoantigens. Cancer Immunology, Immunotherapy, 70, 3291–3302.

    Article  Google Scholar 

  126. Ross, S. L., et al. (2017). Bispecific T cell engager (BiTE®) antibody constructs can mediate bystander tumor cell killing. PLoS ONE, 12(8), e0183390.

    Article  Google Scholar 

  127. Cho, J. H., Collins, J. J., & Wong, W. W. (2018). Universal chimeric antigen receptors for multiplexed and logical control of T cell responses. Cell, 173(6), 1426-1438.e11.

    Article  Google Scholar 

  128. Ventin, M., et al. (2023). B7-H3-targeted CAR T cell activity is enhanced by radiotherapy in solid cancers. Frontiers in Oncology, 13, 1193963.

    Article  Google Scholar 

  129. Bach, P. B., Giralt, S. A., & Saltz, L. B. (2017). FDA approval of tisagenlecleucel: Promise and complexities of a $475 000 cancer drug. JAMA, 318(19), 1861–1862.

    Article  Google Scholar 

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Acknowledgements

The authors would like to thank the Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, for financially supporting this project (grant no.: 64379).

Funding

This study was funded by the Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, and Tabriz University of Medical Sciences (grant no.: 64379).

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Author notes

  1. Hassan Mellatyar and Sina Sattari contributed equally to this work.

Authors and Affiliations

  1. Health Research Center, Chamran Hospital, Tehran, Iran

    Hassan Mellatyar, Sina Sattari & Amir Nezami Asl

  2. Trauma Research Center, Aja University of Medical Sciences, Tehran, Iran

    Amir Nezami Asl

  3. Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Abolfazl Akbarzadeh

Authors
  1. Hassan Mellatyar
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  2. Sina Sattari
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  3. Amir Nezami Asl
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  4. Abolfazl Akbarzadeh
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Contributions

"AA conceptualized research; ANA, and ST supervised research; HM performed research and analyzed data, and prepared figures.All authors reviewed the manuscript."

Corresponding author

Correspondence to Abolfazl Akbarzadeh.

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The ethical approval for this paper was obtained from research ethics committee of Tabriz University of Medical Sciences)IR.TBZMED.VCR.REC.1397.487(.

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Mellatyar, H., Sattari, S., Asl, A.N. et al. Recent Advances and Challenges in Cancer Treatment with Car T Cell Therapy: A Novel Anti-cancer Strategy. BioNanoSci. (2024). https://doi.org/10.1007/s12668-024-01389-x

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