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The potential of CAR T cell therapy for prostate cancer

Nature Reviews Urology volume 18, pages 556–571 (2021)Cite this article

Subjects

Abstract

Chimeric antigen receptor (CAR) T cell immunotherapy involves the genetic modification of the patient’s own T cells so that they specifically recognize and destroy tumour cells. Considerable clinical success has been achieved using this technique in patients with lymphoid malignancies, but clinical studies that investigated treating solid tumours using this emerging technology have been disappointing. A number of developments might be able to increase the efficacy of CAR T cell therapy for treatment of prostate cancer, including improved trafficking to the tumour, techniques to overcome the immunosuppressive tumour microenvironment, as well as methods to enhance CAR T cell persistence, specificity and safety. Furthermore, CAR T cell therapy has the potential to be combined with other treatment modalities, such as androgen deprivation therapy, radiotherapy or chemotherapy, and could be applied as focal CAR T cell therapy for prostate cancer.

Key points

  • Chimeric antigen receptor (CAR) T cells, based on genetic engineering of the patient’s own T cells for targeted tumour cell lysis, have great potential as immunotherapy for prostate cancer.

  • Current developments focus on optimizing CAR T cells to improve trafficking to the tumour, overcome the immunosuppressive tumour microenvironment, and increase the cells’ persistence, specificity and safety.

  • Preclinical studies show that combination with standard therapies, such as androgen deprivation therapy, radiotherapy or chemotherapy, can be used to enhance the efficacy of CAR T cells against prostate cancer.

  • Intratumoural application of CAR T cells based on optimized imaging modalities could provide an effective and safe new focal therapeutic option for patients with localized prostate cancer.

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Fig. 1: Schematic representation of different CAR generations.
Fig. 2: Obstacles to CAR T cell therapy in the tumour microenvironment of prostate cancer.
Fig. 3: Transperineal injection of CAR T cells for focal therapy of prostate cancer.

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Acknowledgements

This work was supported by grants of the Federal Ministry of Education and Research (BMBF-01EO0813 to T.C.), the Horizon 2020 Programme of the European Commission (CARAT-667980 to T.C.), the Federal Ministry of Economic Affairs and Energy (BMWi-03THW15H04 to C.G. and T.C.), and the Research Commission of the Faculty of Medicine of the Albert-Ludwigs-University of Freiburg (no. WOL1111/16 to P.W. and T.C.).

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  1. Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Philipp Wolf, Christian Gratzke & Toni Cathomen

  2. Department of Urology, Medical Center-University of Freiburg, Freiburg, Germany

    Philipp Wolf & Christian Gratzke

  3. Institute for Transfusion Medicine and Gene Therapy, Medical Center-University of Freiburg, Freiburg, Germany

    Jamal Alzubi & Toni Cathomen

  4. Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Freiburg, Germany

    Jamal Alzubi & Toni Cathomen

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T.C. has sponsored research collaborations with Cellectis and serves on the scientific advisory board of Excision BioTherapeutics. The other authors declare no competing interests.

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Wolf, P., Alzubi, J., Gratzke, C. et al. The potential of CAR T cell therapy for prostate cancer. Nat Rev Urol 18, 556–571 (2021). https://doi.org/10.1038/s41585-021-00488-8

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