In vivo CAR engineering for immunotherapy

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  PubMed  CAS  Google Scholar 

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

Article  PubMed  PubMed Central  CAS  Google Scholar 

Mikkilineni, L. & Kochenderfer, J. N. CAR T cell therapies for patients with multiple myeloma. Nat. Rev. Clin. Oncol. 18, 71–84 (2021).

Article  PubMed  CAS  Google Scholar 

Guedan, S., Ruella, M. & June, C. H. Emerging cellular therapies for cancer. Annu. Rev. Immunol. 37, 145–171 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Brudno, J. N. & Kochenderfer, J. N. Chimeric antigen receptor T-cell therapies for lymphoma. Nat. Rev. Clin. Oncol. 15, 31–46 (2018).

Article  PubMed  CAS  Google Scholar 

Amini, L. et al. Preparing for CAR T cell therapy: patient selection, bridging therapies and lymphodepletion. Nat. Rev. Clin. Oncol. 19, 342–355 (2022).

Article  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 

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

Article  PubMed  CAS  Google Scholar 

Depil, S., Duchateau, P., Grupp, S. A., Mufti, G. & Poirot, L. ‘Off-the-shelf’ allogeneic CAR T cells: development and challenges. Nat. Rev. Drug Discov. 19, 185–199 (2020).

Article  PubMed  CAS  Google Scholar 

DiNofia, A. M. & Grupp, S. A. Will allogeneic CAR T cells for CD19(+) malignancies take autologous CAR T cells ‘off the shelf’? Nat. Rev. Clin. Oncol. 18, 195–196 (2021).

Article  PubMed  Google Scholar 

Li, Y.-R. et al. Advancing cell-based cancer immunotherapy through stem cell engineering. Cell Stem Cell 30, 592–610 (2023).

Article  PubMed  PubMed Central  CAS  Google Scholar 

Martin, K. E., Hammer, Q., Perica, K., Sadelain, M. & Malmberg, K.-J. Engineering immune-evasive allogeneic cellular immunotherapies. Nat. Rev. Immunol. 24, 680–693 (2024).

Article  PubMed  CAS  Google Scholar 

Rejeski, K., Jain, M. D., Shah, N. N., Perales, M.-A. & Subklewe, M. Immune effector cell-associated haematotoxicity after CAR T-cell therapy: from mechanism to management. Lancet Haematol. 11, e459–e470 (2024).

Article  PubMed  CAS  Google Scholar 

Tombácz, I. et al. Highly efficient CD4+ T cell targeting and genetic recombination using engineered CD4+ cell-homing mRNA-LNPs. Mol. Ther. 29, 3293–3304 (2021). This preclinical study reports the in vivo CAR engineering of human CD4+T cells using LNP-formulated nucleic acids with high efficiency in humanized mouse models.

Article  PubMed  PubMed Central  Google Scholar 

Kheirolomoom, A. et al. In situ T-cell transfection by anti-CD3-conjugated lipid nanoparticles leads to T-cell activation, migration, and phenotypic shift. Biomaterials 281, 121339 (2022).

Article  PubMed  CAS  Google Scholar 

Huckaby, J. T. et al. Bispecific binder redirected lentiviral vector enables in vivo engineering of CAR-T cells. J. Immunother. Cancer 9, e002737 (2021).

Article  PubMed  PubMed Central  Google Scholar 

Michels, K. R. et al. Preclinical proof of concept for VivoVec, a lentiviral-based platform for in vivo CAR T-cell engineering. J. Immunother. Cancer 11, e006292 (2023).

Article  PubMed  PubMed Central  Google Scholar 

Billingsley, M. M. et al. In vivo mRNA CAR T cell engineering via targeted ionizable lipid nanoparticles with extrahepatic tropism. Small 20, e2304378 (2024).

Article  PubMed  Google Scholar 

Zhou, J.-E. et al. Lipid nanoparticles produce chimeric antigen receptor T cells with interleukin-6 knockdown in vivo. J. Control. Release 350, 298–307 (2022).

Article  PubMed  CAS  Google Scholar 

Rurik, J. G. et al. CAR T cells produced in vivo to treat cardiac injury. Science 375, 91–96 (2022). The first preclinical study to use in vivo CAR engineering of T cells to treat cardiac injury using LNP-formulated nucleic acids.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Pfeiffer, A. et al. In vivo generation of human CD19-CAR T cells results in B-cell depletion and signs of cytokine release syndrome. EMBO Mol. Med. 10, e9158 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Agarwal, S. et al. In vivo generation of CAR T cells selectively in human CD4+ lymphocytes. Mol. Ther. 28, 1783–1794 (2020).

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ho, N. et al. In vivo generation of CAR T cells in the presence of human myeloid cells. Mol. Ther. Methods Clin. Dev. 26, 144–156 (2022).

Article  PubMed  PubMed Central  CAS  Google Scholar 

Agarwal, S., Weidner, T., Thalheimer, F. B. & Buchholz, C. J. In vivo generated human CAR T cells eradicate tumour cells. Oncoimmunology 8, e1671761 (2019).

Article  PubMed  PubMed Central  Google Scholar 

Frank, A. M. et al. Combining T-cell-specific activation and in vivo gene delivery through CD3-targeted lentiviral vectors. Blood Adv. 4, 5702–5715 (2020).

PubMed  PubMed Central  CAS  Google Scholar 

Kebriaei, P. et al. Phase I trials using sleeping beauty to generate CD19-specific CAR T cells. J. Clin. Invest. 126, 3363–3376 (2016).

Article  PubMed  PubMed Central  Google Scholar 

Monjezi, R. et al. Enhanced CAR T-cell engineering using non-viral sleeping beauty transposition from minicircle vectors. Leukemia 31, 186–194 (2017).

Article  PubMed  CAS  Google Scholar 

Liu, Y. et al. In situ MUC1-specific CAR engineering of tumour-supportive macrophages stimulates tumouricidal immunity against pancreatic adenocarcinoma. Nano Today 49, 101805 (2023). A study of combination therapy involving in vivo CAR engineering of intratumoural macrophages and CD47 inhibition.

Article  CAS  Google Scholar 

Yang, Z. et al. Dual mRNA co-delivery for in situ generation of phagocytosis-enhanced CAR macrophages augments hepatocellular carcinoma immunotherapy. J. Control. Release 360, 718–733 (2023).

Article  PubMed  CAS  Google Scholar 

Mukalel, A. J. et al. Oxidized mRNA lipid nanoparticles for in situ chimeric antigen receptor monocyte engineering. Adv. Funct. Mater. 34, 2312038 (2024).

Article  PubMed  CAS  Google Scholar 

Gao, L. et al. Convection-enhanced delivery of nanoencapsulated gene locoregionally yielding ErbB2/Her2-specific CAR-macrophages for brainstem glioma immunotherapy. J. Nanobiotechnology 21, 56 (2023).

Article  PubMed  PubMed Central  CAS  Google Scholar 

Kang, M. et al. Nanocomplex-mediated in vivo programming to chimeric antigen receptor-M1 macrophages for cancer therapy. Adv. Mater. 33, e2103258 (2021). This preclinical study reports a method to in vivo programme macrophages to the M1 phenotype, enabling them to intrinsically penetrate solid tumours and display enhanced antitumour activity.

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