Cytokine IL-36γ improves CAR T-cell functionality and induces endogenous antitumor response Journal Article
| Authors: | Li, X.; Daniyan, A. F.; Lopez, A. V.; Purdon, T. J.; Brentjens, R. J. |
| Article Title: | Cytokine IL-36γ improves CAR T-cell functionality and induces endogenous antitumor response |
| Abstract: | Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable responses in B-cell malignancies. However, many patients suffer from limited response and tumor relapse due to lack of persisting CAR T cells and immune escape. These clinical challenges have compromised the long-term efficacy of CAR T-cell therapy and call for the development of novel CAR designs. We demonstrated that CAR T cells secreting a cytokine interleukin-36γ (IL-36γ) showed significantly improved CAR T-cell expansion and persistence, and resulted in superior tumor eradication compared with conventional CAR T cells. The enhanced cellular function by IL-36γ was mediated through an autocrine manner. In addition, activation of endogenous antigen-presenting cells (APCs) and T cells by IL-36γ aided the formation of a secondary antitumor response, which delayed the progression of antigen-negative tumor challenge. Together, our data provide preclinical evidence to support the translation of this design for an improved CAR T-cell-mediated antitumor response. © 2020, The Author(s), under exclusive licence to Springer Nature Limited. |
| Journal Title: | Leukemia |
| Volume: | 35 |
| Issue: | 2 |
| ISSN: | 0887-6924 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2021-02-01 |
| Start Page: | 506 |
| End Page: | 521 |
| Language: | English |
| DOI: | 10.1038/s41375-020-0874-1 |
| PUBMED: | 32447345 |
| PROVIDER: | scopus |
| PMCID: | PMC7680719 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2021 -- Source: Scopus |
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