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CAR T therapy beyond cancer: the evolution of a living drug

Nature volume 619, pages 707–715 (2023)Cite this article

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Abstract

Engineering a patient’s own T cells to selectively target and eliminate tumour cells has cured patients with untreatable haematologic cancers. These results have energized the field to apply chimaeric antigen receptor (CAR) T therapy throughout oncology. However, evidence from clinical and preclinical studies underscores the potential of CAR T therapy beyond oncology in treating autoimmunity, chronic infections, cardiac fibrosis, senescence-associated disease and other conditions. Concurrently, the deployment of new technologies and platforms provides further opportunity for the application of CAR T therapy to noncancerous pathologies. Here we review the rationale behind CAR T therapy, current challenges faced in oncology, a synopsis of preliminary reports in noncancerous diseases, and a discussion of relevant emerging technologies. We examine potential applications for this therapy in a wide range of contexts. Last, we highlight concerns regarding specificity and safety and outline the path forward for CAR T therapy beyond cancer.

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Fig. 1: CAR T cells are poised to target a wide variety of diseases and pathological substrates.
Fig. 2: CAR T cells are engineered to be precise and powerful killers.
Fig. 3: Advantages of CAR T therapy in other diseases in comparison to cancer.
Fig. 4: A comparison of ex vivo and in vivo platforms being explored for CAR T therapy.

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Acknowledgements

This work was supported by 1P01CA214278 and R01CA226983 (C.H.J.), the Parker Institute for Cancer Immunotherapy and the Centurion Foundation Innovation Fund.

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Authors and Affiliations

  1. Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Daniel J. Baker & Carl H. June

  2. Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Daniel J. Baker & Carl H. June

  3. Parker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA

    Daniel J. Baker & Carl H. June

  4. Cardiovascular Institute, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Daniel J. Baker, Zoltan Arany & Jonathan A. Epstein

  5. Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Zoltan Arany & Jonathan A. Epstein

  6. Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Joseph A. Baur

  7. Institute for Regenerative Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Jonathan A. Epstein

  8. Department of Cell and Developmental Biology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Jonathan A. Epstein

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Contributions

Conceptualization: D.J.B., Z.A., J.A.B., J.A.E., C.H.J. Visualization: D.J.B., Z.A., J.A.B., J.A.E., C.H.J. Writing: D.J.B., Z.A., J.A.B., J.A.E., C.H.J.

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Correspondence to Daniel J. Baker or Carl H. June.

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Competing interests

D.J.B. and Z.A. declare no competing interests. J.A.B. is a consultant to Pfizer and Cytokinetics. J.A.E. is a scientific founder and holds equity in Capstan Therapeutics, which develops therapeutics to reprogram immune cells in vivo. C.H.J. is an inventor on patents and/or patent applications licensed to Novartis Institutes of Biomedical Research and receives licence revenue from such licences. C.H.J. is a scientific founder of Tmunity Therapeutics and Capstan Therapeutics. C.H.J. is a member of the scientific advisory boards of AC Immune, Alaunos, BluesphereBio, Cabaletta, Carisma, Cartography, Cellares, Celldex, Danaher, Decheng, Kite Gilead, Poseida, Verismo, Viracta and WIRB-Copernicus.

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Baker, D.J., Arany, Z., Baur, J.A. et al. CAR T therapy beyond cancer: the evolution of a living drug. Nature 619, 707–715 (2023). https://doi.org/10.1038/s41586-023-06243-w

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