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

Nature Reviews Clinical Oncology volume 21, pages 47–66 (2024)Cite this article

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Abstract

Chimeric antigen receptor (CAR) T cells have been approved for use in patients with B cell malignancies or relapsed and/or refractory multiple myeloma, yet efficacy against most solid tumours remains elusive. The limited imaging and biopsy data from clinical trials in this setting continues to hinder understanding, necessitating a reliance on imperfect preclinical models. In this Perspective, I re-evaluate current data and suggest potential pathways towards greater success, drawing lessons from the few successful trials testing CAR T cells in patients with solid tumours and the clinical experience with tumour-infiltrating lymphocytes. The most promising approaches include the use of pluripotent stem cells, co-targeting multiple mechanisms of immune evasion, employing multiple co-stimulatory domains, and CAR ligand-targeting vaccines. An alternative strategy focused on administering multiple doses of short-lived CAR T cells in an attempt to pre-empt exhaustion and maintain a functional effector pool should also be considered.

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Fig. 1: Targeting barriers to the activity of CAR T cells.
Fig. 2: Injected CAR T cells are highly enriched in central memory T cells compared to circulating T cells.
Fig. 3: CAR T cell persistence in selected trials.
Fig. 4: Lack of functional intratumoural CAR T cells limits antitumour activity.
Fig. 5: Possible strategies to improve the activity of CAR T cells in patients with solid tumours.

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Acknowledgements

The input of A. Bott (Capstan Therapeutics) and J. Fraietta, B. Levine, E. Noguera-Ortega, M. Sellmyer, D. Powell, E. Puré and Z. Xiao (all from the University of Pennsylvania), along with the administrative assistance of M. McNichol are highly appreciated.

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

    Steven M. Albelda

  2. Pulmonary and Critical Care Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Steven M. Albelda

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S.A. has acted as a scientific adviser to Bio4t2 LLC and Verismo Therapeutics, has received research support from Capstan, Novartis and Tmunity and is a founder of Capstan Therapeutics.

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Albelda, S.M. CAR T cell therapy for patients with solid tumours: key lessons to learn and unlearn. Nat Rev Clin Oncol 21, 47–66 (2024). https://doi.org/10.1038/s41571-023-00832-4

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