CAR T cell therapy for patients with solid tumours: key lessons to learn and unlearn

Maude, S. L. et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N. Engl. J. Med. 371, 1507–1517 (2014).

Article  PubMed Central  PubMed  Google Scholar 

June, C. H. & Sadelain, M. Chimeric antigen receptor therapy. N. Engl. J. Med. 379, 64–73 (2018).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Majzner, R. G. & Mackall, C. L. Clinical lessons learned from the first leg of the CAR T cell journey. Nat. Med. 25, 1341–1355 (2019).

Article  CAS  PubMed  Google Scholar 

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

Article  PubMed  Google Scholar 

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

Article  PubMed  Google Scholar 

Rosenberg, S. A. & Restifo, N. P. Adoptive cell transfer as personalized immunotherapy for human cancer. Science 348, 62–68 (2015).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Betof Warner, A., Corrie, P. G. & Hamid, O. Tumor-infiltrating lymphocyte therapy in melanoma: facts to the future. Clin. Cancer Res. 29, 1835–1854 (2023).

Article  PubMed  Google Scholar 

Adami, A. & Maher, J. An overview of CAR T-cell clinical trial activity to 2021. Immunother. Adv. 1, ltab004 (2021).

Article  PubMed Central  PubMed  Google Scholar 

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

Article  PubMed  Google Scholar 

Labanieh, L. & Mackall, C. L. CAR immune cells: design principles, resistance and the next generation. Nature 614, 635–648 (2023).

Article  CAS  PubMed  Google Scholar 

Newick, K., O’Brien, S., Moon, E. & Albelda, S. M. CAR T cell therapy for solid tumors. Annu. Rev. Med. 68, 139–152 (2017).

Article  CAS  PubMed  Google Scholar 

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

Article  CAS  PubMed Central  PubMed  Google Scholar 

Knochelmann, H. M. et al. CAR T cells in solid tumors: blueprints for building effective therapies. Front. Immunol. 9, 1740 (2018).

Article  PubMed Central  PubMed  Google Scholar 

Martinez, M. & Moon, E. K. CAR T cells for solid tumors: new strategies for finding, infiltrating, and surviving in the tumor microenvironment. Front. Immunol. 10, 128 (2019).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Rafiq, S., Hackett, C. S. & Brentjens, R. J. Engineering strategies to overcome the current roadblocks in CAR T cell therapy. Nat. Rev. Clin. Oncol. 17, 147–167 (2020).

Article  PubMed  Google Scholar 

Wagner, J., Wickman, E., DeRenzo, C. & Gottschalk, S. CAR T cell therapy for solid tumors: bright future or dark reality? Mol. Ther. 28, 2320–2339 (2020).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Tantalo, D. G. et al. Understanding T cell phenotype for the design of effective chimeric antigen receptor T cell therapies. J. Immunother. Cancer 9, e002555 (2021).

Article  PubMed Central  PubMed  Google Scholar 

Gumber, D. & Wang, L. D. Improving CAR-T immunotherapy: overcoming the challenges of T cell exhaustion. EBioMedicine 77, 103941 (2022).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Lopez-Cantillo, G., Uruena, C., Camacho, B. A. & Ramirez-Segura, C. CAR-T cell performance: how to improve their persistence? Front. Immunol. 13, 878209 (2022).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Drougkas, K. et al. Comprehensive clinical evaluation of CAR-T cell immunotherapy for solid tumors: a path moving forward or a dead end? J. Cancer Res. Clin. Oncol. 149, 2709–2734 (2023).

Article  PubMed  Google Scholar 

Maher, J. & Davies, D. M. CAR-based immunotherapy of solid tumours – a survey of the emerging targets. Cancers 15, 1171 (2023).

Article  CAS  PubMed Central  PubMed  Google Scholar 

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

Article  CAS  PubMed Central  PubMed  Google Scholar 

Maus, M. V. et al. T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol. Res. 1, 26–31 (2013).

Article  CAS  PubMed Central  PubMed  Google Scholar 

O’Rourke, D. M. 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. 9, eaaa0984 (2017).

Article  PubMed Central  PubMed  Google Scholar 

Haas, A. R. et al. Phase I study of lentiviral-transduced chimeric antigen receptor-modified T cells recognizing mesothelin in advanced solid cancers. Mol. Ther. 27, 1919–1929 (2019).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Narayan, V. et al. PSMA-targeting TGFβ-insensitive armored CAR T cells in metastatic castration-resistant prostate cancer: a phase 1 trial. Nat. Med. 28, 724–734 (2022).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Gargett, T. et al. GD2-specific CAR T cells undergo potent activation and deletion following antigen encounter but can be protected from activation-induced cell death by PD-1 blockade. Mol. Ther. 24, 1135–1149 (2016).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Brown, C. E. et al. Regression of glioblastoma after chimeric antigen receptor T-cell therapy. N. Engl. J. Med. 375, 2561–2569 (2016).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Majzner, R. G. et al. GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature 603, 934–941 (2022).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Qi, C. et al. Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results. Nat. Med. 28, 1189–1198 (2022).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Del Bufalo, F. et al. GD2-CART01 for relapsed or refractory high-risk neuroblastoma. N. Engl. J. Med. 388, 1284–1295 (2023).

Article  Google Scholar 

Box, G. E. P. Science and statistics. J. Am. Stat. Assoc. 71, 791–799 (1976).

Article  Google Scholar 

Duncan, B. B., Dunbar, C. E. & Ishii, K. Applying a clinical lens to animal models of CAR-T cell therapies. Mol. Ther. Methods Clin. Dev. 27, 17–31 (2022).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Klampatsa, A. et al. Analysis and augmentation of the immunologic bystander effects of CAR T cell therapy in a syngeneic mouse cancer model. Mol. Ther. Oncolytics 18, 360–371 (2020).

Article  CAS  PubMed Central  PubMed  Google Scholar 

Srivastava, S. et al. Immunogenic chemotherapy enhances recruitment of CAR-T cells to lung tumors and improves antitumor efficacy when combined with checkpoint blockade. Cancer Cell 39, 193–208.e10 (2021).

Article  CAS  PubMed  Google Scholar 

Chmielewski, M. & Abken, H. CAR T cells releasing IL-18 convert to T-bethigh FoxO1low effectors that exhibit augmented activity against advanced solid tumors. Cell Rep. 21, 3205–3219 (2017).

Article  CAS  PubMed  Google Scholar 

Mhaidly, R. & Verhoeyen, E. Humanized mice are precious tools for preclinical evaluation of CAR T and CAR NK cell therapies. Cancers 12, 1915 (2020).

Article  CAS 

Comments (0)

No login
gif