June, C. H., O’Connor, R. S., Kawalekar, O. U., Ghassemi, S. & Milone, M. C. CAR-T cell immunotherapy for human cancer. Science 359, 1361–1365 (2018).
Rodriguez-Otero, P. et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N. Engl. J. Med. 388, 1002–1014 (2023).
San-Miguel, J. et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N. Engl. J. Med. 389, 335–347 (2023).
Ruella, M., Korell, F., Porazzi, P. & Maus, M. V. Mechanisms of resistance to chimeric antigen receptor-T cells in haematological malignancies. Nat. Rev. Drug Discov. 22, 976–995 (2023).
Munshi, N. C. et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N. Engl. J. Med. 384, 705–716 (2021).
Berdeja, J. G. et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet 398, 314–324 (2021).
Schmidt, R. et al. CRISPR activation and interference screens decode stimulation responses in primary human T cells. Science 375, eabj4008 (2022).
Wu, J. E. et al. In vitro modeling of CD8+ T cell exhaustion enables CRISPR screening to reveal a role for BHLHE40. Sci. Immunol. 8, eade3369 (2023).
Shang, W. et al. Genome-wide CRISPR screen identifies FAM49B as a key regulator of actin dynamics and T cell activation. Proc. Natl Acad. Sci. USA 115, E4051–E4060 (2018).
Simeonov, D. R. & Marson, A. CRISPR-based tools in immunity. Annu. Rev. Immunol. 37, 571–597 (2019).
Wang, D. et al. CRISPR screening of CAR-T cells and cancer stem cells reveals critical dependencies for cell-based therapies. Cancer Discov. 11, 1192–1211 (2021).
Shifrut, E. et al. Genome-wide CRISPR screens in primary human T cells reveal key regulators of immune function. Cell 175, 1958–1971 (2018).
Carnevale, J. et al. RASA2 ablation in T cells boosts antigen sensitivity and long-term function. Nature 609, 174–182 (2022).
Freitas, K. A. et al. Enhanced T cell effector activity by targeting the Mediator kinase module. Science 378, eabn5647 (2022).
Chen, Z. et al. In vivo CD8+ T cell CRISPR screening reveals control by Fli1 in infection and cancer. Cell 184, 1262–1280 (2021).
Wei, J. et al. Targeting REGNASE-1 programs long-lived effector T cells for cancer therapy. Nature 576, 471–476 (2019).
Lynn, R. C. et al. c-Jun overexpression in CAR T cells induces exhaustion resistance. Nature 576, 293–300 (2019).
Friedman, K. M. et al. Effective targeting of multiple B-cell maturation antigen-expressing hematological malignances by anti-B-cell maturation antigen chimeric antigen receptor T cells. Hum. Gene Ther. 29, 585–601 (2018).
Stock, S., Schmitt, M. & Sellner, L. Optimizing manufacturing protocols of chimeric antigen receptor T cells for improved anticancer immunotherapy. Int. J. Mol. Sci. 20, 6223 (2019).
Locke, F. L. et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1–2 trial. Lancet Oncol. 20, 31–42 (2019).
Xu, Y. et al. Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15. Blood 123, 3750–3759 (2014).
Cieri, N. et al. IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors. Blood 121, 573–584 (2013).
Dwyer, C. J. et al. Fueling cancer immunotherapy with common γ chain cytokines. Front. Immunol. 10, 263 (2019).
Abou-El-Enein, M. et al. Scalable manufacturing of CAR T cells for cancer immunotherapy. Blood Cancer Discov. 2, 408–422 (2021).
Amatya, C. et al. Optimization of anti-CD19 CAR T cell production for treatment of patients with chronic lymphocytic leukemia. Mol. Ther. Methods Clin. Dev. 32, 101212 (2024).
Lane-Reticker, S. K. et al. Protocol for in vivo CRISPR screening using selective CRISPR antigen removal lentiviral vectors. STAR Protoc. 4, 102082 (2023).
Liau, N. P. D. et al. The molecular basis of JAK/STAT inhibition by SOCS1. Nat. Commun. 9, 1558 (2018).
Sporri, B., Kovanen, P. E., Sasaki, A., Yoshimura, A. & Leonard, W. J. JAB/SOCS1/SSI-1 is an interleukin-2-induced inhibitor of IL-2 signaling. Blood 97, 221–226 (2001).
Flosbach, M. et al. PTPN2 deficiency enhances programmed T cell expansion and survival capacity of activated T cells. Cell Rep. 32, 107957 (2020).
Simoncic, P. D., Lee-Loy, A., Barber, D. L., Tremblay, M. L. & McGlade, C. J. The T cell protein tyrosine phosphatase is a negative regulator of Janus family kinases 1 and 3. Curr. Biol. 12, 446–453 (2002).
Matsushita, K. et al. Zc3h12a is an RNase essential for controlling immune responses by regulating mRNA decay. Nature 458, 1185–1190 (2009).
Mino, T. et al. Regnase-1 and roquin regulate a common element in inflammatory mRNAs by spatiotemporally distinct mechanisms. Cell 161, 1058–1073 (2015).
Behrens, G. et al. Disrupting roquin-1 interaction with regnase-1 induces autoimmunity and enhances antitumor responses. Nat. Immunol. 22, 1563–1576 (2021).
Uehata, T. et al. Malt1-induced cleavage of regnase-1 in CD4+ helper T cells regulates immune activation. Cell 153, 1036–1049 (2013).
Kloss, C. C. et al. Dominant-negative TGF-β receptor enhances PSMA-targeted human CAR T cell proliferation and augments prostate cancer eradication. Mol. Ther. 26, 1855–1866 (2018).
Larson, R. C. et al. Anti-TACI single and dual-targeting CAR T cells overcome BCMA antigen loss in multiple myeloma. Nat. Commun. 14, 7509 (2023).
Lemoine, J., Ruella, M. & Houot, R. Overcoming intrinsic resistance of cancer cells to CAR T-cell killing. Clin. Cancer Res. 27, 6298–6306 (2021).
Razavipour, S. F., Harikumar, K. B. & Slingerland, J. M. p27 as a transcriptional regulator: new roles in development and cancer. Cancer Res. 80, 3451–3458 (2020).
Harrison, S. J. et al. CAR+ T-cell lymphoma post ciltacabtagene autoleucel therapy for relapsed refractory multiple myeloma. Blood 142, 6939 (2023).
Perica, K. et al. CD4+ T-cell lymphoma harboring a chimeric antigen receptor integration in TP53. N. Engl. J. Med. 392, 577–583 (2025).
Ghilardi, G. et al. T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy. Nat. Med. 30, 984–989 (2024).
Larson, R. C. & Maus, M. V. Recent advances and discoveries in the mechanisms and functions of CAR T cells. Nat. Rev. Cancer 21, 145–161 (2021).
Zheng, W. et al. Regnase-1 suppresses TCF-1+ precursor exhausted T-cell formation to limit CAR-T-cell responses against ALL. Blood 138, 122–135 (2021).
LaFleur, M. W. et al. A CRISPR–Cas9 delivery system for in vivo screening of genes in the immune system. Nat. Commun. 10, 1668 (2019).
LaFleur, M. W. et al. PTPN2 regulates the generation of exhausted CD8+ T cell subpopulations and restrains tumor immunity. Nat. Immunol. 20, 1335–1347 (2019).
Lin, C.-P. et al. Multimodal stimulation screens reveal unique and shared genes limiting T cell fitness. Cancer Cell 42, 623–645 (2024).
Li, R. et al. Comparative optimization of combinatorial CRISPR screens. Nat. Commun. 13, 2469 (2022).
Tirosh, I. et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352, 189–196 (2016).
