Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling-Reference-Cited by-同舟云学术

Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling

Published:2021-04-02 Issue:6537 Volume:372 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Weber Evan W.¹^ORCID,Parker Kevin R.²^ORCID,Sotillo Elena¹,Lynn Rachel C.¹^ORCID,Anbunathan Hima¹^ORCID,Lattin John¹,Good Zinaida¹³⁴^ORCID,Belk Julia A.⁵^ORCID,Daniel Bence⁶^ORCID,Klysz Dorota¹^ORCID,Malipatlolla Meena¹,Xu Peng¹,Bashti Malek¹,Heitzeneder Sabine¹^ORCID,Labanieh Louai¹^ORCID,Vandris Panayiotis¹^ORCID,Majzner Robbie G.¹⁷^ORCID,Qi Yanyan²,Sandor Katalin⁶^ORCID,Chen Ling-Chun⁸,Prabhu Snehit¹^ORCID,Gentles Andrew J.⁹,Wandless Thomas J.⁸,Satpathy Ansuman T.²³⁶^ORCID,Chang Howard Y.²³⁶¹⁰^ORCID,Mackall Crystal L.¹³⁷¹¹^ORCID

Affiliation:

1. Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.

2. Department of Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, CA 94305, USA.

3. Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA.

4. Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA 94305, USA.

5. Department of Computer Science, Stanford University, Stanford, CA 94305, USA.

6. Department of Pathology, Stanford University, Stanford, CA 94305, USA.

7. Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.

8. Department of Chemical and Systems Biology, Stanford University, CA 94305, USA.

9. Department of Biomedical Informatics Research, Stanford University School of Medicine, Stanford, CA 94305, USA.

10. Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.

11. Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.

Abstract

CAR-T cells rest to get back in the race Chimeric antigen receptor (CAR)–T cells, which are engineered to target specific tumor antigens, are increasingly used as an immunotherapy. CAR-T cells have shown promising results in patients, particularly in hematologic cancers, but their anticancer activity can be limited by the onset of exhaustion and the loss of effectiveness. Weber et al. characterized the phenotypic and epigenomic changes associated with CAR-T cell exhaustion caused by continuous activity and the beneficial effects of transient rest periods (see the Perspective by Mamonkin and Brenner). The authors tested different approaches for providing these rest periods, such as using the drug dasatinib to temporarily suppress T cell activity, which helped to prevent exhaustion and improved antitumor activity in mouse models. Science , this issue p. eaba1786 ; see also p. 34

Funder

National Science Foundation

National Institutes of Health

Howard Hughes Medical Institute

National Institute of Allergy and Infectious Diseases

Teikyo University School of Medicine

Parker Institute for Cancer Immunotherapy

Stanford University School of Medicine

Stand Up To Cancer

Virginia and D.K. Ludwig Fund for Cancer Research

Burroughs Wellcome Fund

Stanford University