CAR-T Cell Therapy and the Gut Microbiota

Sahana Asokan; Nyssa Cullin; Christoph K Stein-Thoeringer; Eran Elinav

doi:10.3390/cancers15030794

CAR-T Cell Therapy and the Gut Microbiota

Sahana Asokan, Nyssa Cullin, Christoph K Stein-Thoeringer^*, Eran Elinav^*

^*Corresponding author for this work

Department of Systems Immunology

Research output: Contribution to journal › Review article › peer-review

22 Citations (Scopus)

Abstract

Chimeric antigen receptor (CAR) - T cell cancer therapy has yielded promising results in treating hematologic malignancies in clinical studies, and a growing number of CAR-T regimens are approved for clinical usage. While the therapy is considered of great potential in expanding the cancer immunotherapy arsenal, more than half of patients receiving CAR-T infusions do not respond, while others develop significant adverse effects, collectively indicating a need for optimization of CAR-T treatment to the individual. The microbiota is increasingly suggested as a major modulator of immunotherapy responsiveness. Studying causal microbiota roles possibly contributing to CAR-T therapy efficacy, adverse effects reduction, and prediction of patient responsiveness constitutes an exciting area of active research. Herein, we discuss the latest developments implicating human microbiota involvement in CAR-T therapy, while highlighting challenges and promises in harnessing the microbiota as a predictor and modifier of CAR-T treatment towards optimized efficacy and minimization of treatment-related adverse effects.

Original language	English
Article number	794
Journal	Cancers
Volume	15
Issue number	3
Early online date	28 Jan 2023
DOIs	https://doi.org/10.3390/cancers15030794
Publication status	Published - Feb 2023

Funding

We thank the members of the Division of Microbiome and Cancer, DKFZ and ElinavLab, Weizmann Institute of Science, for insightful discussions; C.K.S-T. is supported by the German José Carreras Leukemia Foundation (01 R/2020), the German Research Foundation (DFG) (STE 2964/5-1), and the Baden-Württemberg Stiftung. E.E. is supported by the Leona M. and Harry B. Helmsley Charitable Trust, Adelis Foundation, Pearl Welinsky Merlo Scientific Progress Research Fund, Park Avenue Charitable Fund, Hanna and Dr. Ludwik Wallach Cancer Research Fund, Daniel Morris Trust, Wolfson Family Charitable Trust and Wolfson Foundation, Ben B. and Joyce E. Eisenberg Foundation, White Rose International Foundation, Estate of Malka Moskowitz, Estate of Myron H. Ackerman, Estate of Bernard Bishin for the WIS-Clalit Program, Else Kröener-Fresenius Foundation, Jeanne and Joseph Nissim Center for Life Sciences Research, A. Moussaieff, M. de Botton, Vainboim family, A. Davidoff, the V. R. Schwartz Research Fellow Chair and by grants funded by the European Research Council, Israel Science Foundation, Israel Ministry of Science and Technology, Israel Ministry of Health, Helmholtz Foundation, Garvan Institute of Medical Research, European Crohn’s and Colitis Organization, Deutsch-Israelische Projektkooperation, IDSA Foundation, and Wellcome Trust. E.E. is the incumbent of the Sir Marc and Lady Tania Feldmann Professorial Chair, a senior fellow of the Canadian Institute of Advanced Research, and an international scholar of the Bill & Melinda Gates Foundation and Howard Hughes Medical Institute. Publisher Copyright: © 2023 by the authors.

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

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title = "CAR-T Cell Therapy and the Gut Microbiota",

abstract = "Chimeric antigen receptor (CAR) - T cell cancer therapy has yielded promising results in treating hematologic malignancies in clinical studies, and a growing number of CAR-T regimens are approved for clinical usage. While the therapy is considered of great potential in expanding the cancer immunotherapy arsenal, more than half of patients receiving CAR-T infusions do not respond, while others develop significant adverse effects, collectively indicating a need for optimization of CAR-T treatment to the individual. The microbiota is increasingly suggested as a major modulator of immunotherapy responsiveness. Studying causal microbiota roles possibly contributing to CAR-T therapy efficacy, adverse effects reduction, and prediction of patient responsiveness constitutes an exciting area of active research. Herein, we discuss the latest developments implicating human microbiota involvement in CAR-T therapy, while highlighting challenges and promises in harnessing the microbiota as a predictor and modifier of CAR-T treatment towards optimized efficacy and minimization of treatment-related adverse effects. ",

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AB - Chimeric antigen receptor (CAR) - T cell cancer therapy has yielded promising results in treating hematologic malignancies in clinical studies, and a growing number of CAR-T regimens are approved for clinical usage. While the therapy is considered of great potential in expanding the cancer immunotherapy arsenal, more than half of patients receiving CAR-T infusions do not respond, while others develop significant adverse effects, collectively indicating a need for optimization of CAR-T treatment to the individual. The microbiota is increasingly suggested as a major modulator of immunotherapy responsiveness. Studying causal microbiota roles possibly contributing to CAR-T therapy efficacy, adverse effects reduction, and prediction of patient responsiveness constitutes an exciting area of active research. Herein, we discuss the latest developments implicating human microbiota involvement in CAR-T therapy, while highlighting challenges and promises in harnessing the microbiota as a predictor and modifier of CAR-T treatment towards optimized efficacy and minimization of treatment-related adverse effects.

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CAR-T Cell Therapy and the Gut Microbiota

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