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).

Article  CAS  PubMed  Google Scholar 

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

Article  PubMed  PubMed Central  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 

Finck, A. V., Blanchard, T., Roselle, C. P., Golinelli, G. & June, C. H. Engineered cellular immunotherapies in cancer and beyond. Nat. Med. 28, 678–689 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Benjamin, R. et al. Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B cell acute lymphoblastic leukaemia: results of two phase 1 studies. Lancet 396, 1885–1894 (2020).

Article  CAS  PubMed  Google Scholar 

van der Stegen, S. J. C. et al. Generation of T cell-receptor-negative CD8αβ-positive CAR T cells from T cell-derived induced pluripotent stem cells. Nat. Biomed. Eng. 6, 1284–1297 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Liu, E. et al. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. N. Engl. J. Med. 382, 545–553 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Heczey, A. et al. Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: an interim analysis. Nat. Med. 26, 1686–1690 (2020).

Article  CAS  PubMed  Google Scholar 

Klichinsky, M. et al. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat. Biotechnol. 38, 947–953 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Godfrey, D. I., Le Nours, J., Andrews, D. M., Uldrich, A. P. & Rossjohn, J. Unconventional T cell targets for cancer immunotherapy. Immunity 48, 453–473 (2018).

Article  CAS  PubMed  Google Scholar 

Chandra, S. & Kronenberg, M. Activation and function of iNKT and MAIT cells. Adv. Immunol. 127, 145–201 (2015).

Article  CAS  PubMed  Google Scholar 

Chaidos, A. et al. Graft invariant natural killer T cell dose predicts risk of acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation. Blood 119, 5030–5036 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Exley, M. A. et al. Adoptive transfer of invariant NKT cells as immunotherapy for advanced melanoma: a phase I clinical trial. Clin. Cancer Res. 23, 3510–3519 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bae, E. A. et al. Activation of NKT cells in an anti-PD-1-resistant tumor model enhances antitumor immunity by reinvigorating exhausted CD8 T cells. Cancer Res. 78, 5315–5326 (2018).

Article  CAS  PubMed  Google Scholar 

Varghese, B. et al. Invariant NKT cell-augmented GM-CSF-secreting tumor vaccine is effective in advanced prostate cancer model. Cancer Immunol. Immunother. 71, 2943–2955 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lynch, L. et al. Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production. Immunity 37, 574–587 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brennan, P. J., Brigl, M. & Brenner, M. B. Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions. Nat. Rev. Immunol. 13, 101–117 (2013).

Article  CAS  PubMed  Google Scholar 

Li, Y.-R. et al. Profiling ovarian cancer tumor and microenvironment during disease progression for cell-based immunotherapy design. iScience 26, 107952 (2023).

Article  PubMed  PubMed Central  Google Scholar 

Li, Y.-R. et al. Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy. Cell Rep. Med. 2, 100449 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Rotolo, A. et al. Enhanced anti-lymphoma activity of CAR19-iNKT cells underpinned by dual CD19 and CD1d targeting. Cancer Cell 34, 596–610.e11 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Landoni, E. et al. IL-12 reprograms CAR-expressing natural killer T cells to long-lived Th1-polarized cells with potent antitumor activity. Nat. Commun. 15, 89 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xu, X. et al. NKT cells coexpressing a GD2-specific chimeric antigen receptor and IL15 show enhanced in vivo persistence and antitumor activity against neuroblastoma. Clin. Cancer Res. 25, 7126–7138 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu, Y. et al. IL-21-armored B7H3 CAR-iNKT cells exert potent antitumor effects. iScience 27, 108597 (2024).

Article  CAS  PubMed  Google Scholar 

Heczey, A. et al. Anti-GD2 CAR-NKT cells in relapsed or refractory neuroblastoma: updated phase 1 trial interim results. Nat. Med. 29, 1379–1388 (2023).

Article  CAS  PubMed  Google Scholar 

Li, Y.-R. et al. Generation of allogeneic CAR-NKT cells from hematopoietic stem and progenitor cells using a clinically guided culture method. Nat. Biotechnol. https://doi.org/10.1038/s41587-024-02226-y (2024).

Article  PubMed  PubMed Central  Google Scholar 

Li, Y.-R. et al. Engineering allorejection-resistant CAR-NKT cells from hematopoietic stem cells for off-the-shelf cancer immunotherapy. Mol. Ther. 32, 1849–1874 (2024).

Article  CAS  PubMed  Google Scholar 

Labanieh, L., Majzner, R. G. & Mackall, C. L. Programming CAR-T cells to kill cancer. Nat. Biomed. Eng. 2, 377–391 (2018).

Article  CAS  PubMed  Google Scholar 

Park, J. H., Geyer, M. B. & Brentjens, R. J. CD19-targeted CAR T-cell therapeutics for hematologic malignancies: interpreting clinical outcomes to date. Blood 127, 3312–3320 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Teoh, P. J. & Chng, W. J. CAR T-cell therapy in multiple myeloma: more room for improvement. Blood Cancer J. 11, 84 (2021).

Article  PubMed  PubMed Central  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