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4-1BB-Based CAR T Cells Effectively Reverse Exhaustion and Enhance the Anti-Tumor Immune Response through Autocrine PD-L1 scFv Antibody
Exhaustion of chimeric antigen receptor (CAR) T cells is one of the limitations for CAR T efficacy in solid tumors and for tumor recurrence after initial CAR T treatment. Tumor treatment with a combination of programmed cell death receptor-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blockage and...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961031/ https://www.ncbi.nlm.nih.gov/pubmed/36835603 http://dx.doi.org/10.3390/ijms24044197 |
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author | Cheng, Kang Feng, Xiangming Chai, Zhirong Wang, Zhenzhen Liu, Zheng Yan, Zhanchao Wang, Yanming Zhang, Shoutao |
author_facet | Cheng, Kang Feng, Xiangming Chai, Zhirong Wang, Zhenzhen Liu, Zheng Yan, Zhanchao Wang, Yanming Zhang, Shoutao |
author_sort | Cheng, Kang |
collection | PubMed |
description | Exhaustion of chimeric antigen receptor (CAR) T cells is one of the limitations for CAR T efficacy in solid tumors and for tumor recurrence after initial CAR T treatment. Tumor treatment with a combination of programmed cell death receptor-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blockage and CD28-based CAR T cells has been intensively studied. However, it remains largely unclear whether autocrine single-chain variable fragments (scFv) PD-L1 antibody can improve 4-1BB-based CAR T cell anti-tumor activity and revert CAR T cell exhaustion. Here, we studied T cells engineered with autocrine PD-L1 scFv and 4-1BB-containing CAR. The antitumor activity and exhaustion of CAR T cells were investigated in vitro and in a xenograft cancer model using NCG mice. CAR T cells with autocrine PD-L1 scFv antibody demonstrate enhanced anti-tumor activity in solid tumors and hematologic malignancies by blocking the PD-1/PD-L1 signaling. Importantly, we found that CAR T exhaustion was largely diminished by autocrine PD-L1 scFv antibody in vivo. As such, 4-1BB CAR T with autocrine PD-L1 scFv antibody combined the power of CAR T cells and the immune checkpoint inhibitor, thereby increasing the anti-tumor immune function and CAR T persistence, providing a cell therapy solution for a better clinical outcome. |
format | Online Article Text |
id | pubmed-9961031 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99610312023-02-26 4-1BB-Based CAR T Cells Effectively Reverse Exhaustion and Enhance the Anti-Tumor Immune Response through Autocrine PD-L1 scFv Antibody Cheng, Kang Feng, Xiangming Chai, Zhirong Wang, Zhenzhen Liu, Zheng Yan, Zhanchao Wang, Yanming Zhang, Shoutao Int J Mol Sci Article Exhaustion of chimeric antigen receptor (CAR) T cells is one of the limitations for CAR T efficacy in solid tumors and for tumor recurrence after initial CAR T treatment. Tumor treatment with a combination of programmed cell death receptor-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blockage and CD28-based CAR T cells has been intensively studied. However, it remains largely unclear whether autocrine single-chain variable fragments (scFv) PD-L1 antibody can improve 4-1BB-based CAR T cell anti-tumor activity and revert CAR T cell exhaustion. Here, we studied T cells engineered with autocrine PD-L1 scFv and 4-1BB-containing CAR. The antitumor activity and exhaustion of CAR T cells were investigated in vitro and in a xenograft cancer model using NCG mice. CAR T cells with autocrine PD-L1 scFv antibody demonstrate enhanced anti-tumor activity in solid tumors and hematologic malignancies by blocking the PD-1/PD-L1 signaling. Importantly, we found that CAR T exhaustion was largely diminished by autocrine PD-L1 scFv antibody in vivo. As such, 4-1BB CAR T with autocrine PD-L1 scFv antibody combined the power of CAR T cells and the immune checkpoint inhibitor, thereby increasing the anti-tumor immune function and CAR T persistence, providing a cell therapy solution for a better clinical outcome. MDPI 2023-02-20 /pmc/articles/PMC9961031/ /pubmed/36835603 http://dx.doi.org/10.3390/ijms24044197 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cheng, Kang Feng, Xiangming Chai, Zhirong Wang, Zhenzhen Liu, Zheng Yan, Zhanchao Wang, Yanming Zhang, Shoutao 4-1BB-Based CAR T Cells Effectively Reverse Exhaustion and Enhance the Anti-Tumor Immune Response through Autocrine PD-L1 scFv Antibody |
title | 4-1BB-Based CAR T Cells Effectively Reverse Exhaustion and Enhance the Anti-Tumor Immune Response through Autocrine PD-L1 scFv Antibody |
title_full | 4-1BB-Based CAR T Cells Effectively Reverse Exhaustion and Enhance the Anti-Tumor Immune Response through Autocrine PD-L1 scFv Antibody |
title_fullStr | 4-1BB-Based CAR T Cells Effectively Reverse Exhaustion and Enhance the Anti-Tumor Immune Response through Autocrine PD-L1 scFv Antibody |
title_full_unstemmed | 4-1BB-Based CAR T Cells Effectively Reverse Exhaustion and Enhance the Anti-Tumor Immune Response through Autocrine PD-L1 scFv Antibody |
title_short | 4-1BB-Based CAR T Cells Effectively Reverse Exhaustion and Enhance the Anti-Tumor Immune Response through Autocrine PD-L1 scFv Antibody |
title_sort | 4-1bb-based car t cells effectively reverse exhaustion and enhance the anti-tumor immune response through autocrine pd-l1 scfv antibody |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961031/ https://www.ncbi.nlm.nih.gov/pubmed/36835603 http://dx.doi.org/10.3390/ijms24044197 |
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