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Universal redirection of CAR T cells against solid tumours via membrane-inserted ligands for the CAR
The effectiveness of chimaeric antigen receptor (CAR) T cell therapies for solid tumours is hindered by difficulties in the selection of an effective target antigen, owing to the heterogeneous expression of tumour antigens and to target antigen expression in healthy tissues. Here we show that T cell...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10504084/ https://www.ncbi.nlm.nih.gov/pubmed/37291434 http://dx.doi.org/10.1038/s41551-023-01048-8 |
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author | Zhang, Angela Q. Hostetler, Alexander Chen, Laura E. Mukkamala, Vainavi Abraham, Wuhbet Padilla, Lucia T. Wolff, Alexandra N. Maiorino, Laura Backlund, Coralie M. Aung, Aereas Melo, Mariane Li, Na Wu, Shengwei Irvine, Darrell J. |
author_facet | Zhang, Angela Q. Hostetler, Alexander Chen, Laura E. Mukkamala, Vainavi Abraham, Wuhbet Padilla, Lucia T. Wolff, Alexandra N. Maiorino, Laura Backlund, Coralie M. Aung, Aereas Melo, Mariane Li, Na Wu, Shengwei Irvine, Darrell J. |
author_sort | Zhang, Angela Q. |
collection | PubMed |
description | The effectiveness of chimaeric antigen receptor (CAR) T cell therapies for solid tumours is hindered by difficulties in the selection of an effective target antigen, owing to the heterogeneous expression of tumour antigens and to target antigen expression in healthy tissues. Here we show that T cells with a CAR specific for fluorescein isothiocyanate (FITC) can be directed against solid tumours via the intratumoural administration of a FITC-conjugated lipid–poly(ethylene)-glycol amphiphile that inserts itself into cell membranes. In syngeneic and human tumour xenografts in mice, ‘amphiphile tagging’ of tumour cells drove tumour regression via the proliferation and accumulation of FITC-specific CAR T cells in the tumours. In syngeneic tumours, the therapy induced the infiltration of host T cells, elicited endogenous tumour-specific T cell priming and led to activity against distal untreated tumours and to protection against tumour rechallenge. Membrane-inserting ligands for specific CARs may facilitate the development of adoptive cell therapies that work independently of antigen expression and of tissue of origin. |
format | Online Article Text |
id | pubmed-10504084 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-105040842023-09-17 Universal redirection of CAR T cells against solid tumours via membrane-inserted ligands for the CAR Zhang, Angela Q. Hostetler, Alexander Chen, Laura E. Mukkamala, Vainavi Abraham, Wuhbet Padilla, Lucia T. Wolff, Alexandra N. Maiorino, Laura Backlund, Coralie M. Aung, Aereas Melo, Mariane Li, Na Wu, Shengwei Irvine, Darrell J. Nat Biomed Eng Article The effectiveness of chimaeric antigen receptor (CAR) T cell therapies for solid tumours is hindered by difficulties in the selection of an effective target antigen, owing to the heterogeneous expression of tumour antigens and to target antigen expression in healthy tissues. Here we show that T cells with a CAR specific for fluorescein isothiocyanate (FITC) can be directed against solid tumours via the intratumoural administration of a FITC-conjugated lipid–poly(ethylene)-glycol amphiphile that inserts itself into cell membranes. In syngeneic and human tumour xenografts in mice, ‘amphiphile tagging’ of tumour cells drove tumour regression via the proliferation and accumulation of FITC-specific CAR T cells in the tumours. In syngeneic tumours, the therapy induced the infiltration of host T cells, elicited endogenous tumour-specific T cell priming and led to activity against distal untreated tumours and to protection against tumour rechallenge. Membrane-inserting ligands for specific CARs may facilitate the development of adoptive cell therapies that work independently of antigen expression and of tissue of origin. Nature Publishing Group UK 2023-06-08 2023 /pmc/articles/PMC10504084/ /pubmed/37291434 http://dx.doi.org/10.1038/s41551-023-01048-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Zhang, Angela Q. Hostetler, Alexander Chen, Laura E. Mukkamala, Vainavi Abraham, Wuhbet Padilla, Lucia T. Wolff, Alexandra N. Maiorino, Laura Backlund, Coralie M. Aung, Aereas Melo, Mariane Li, Na Wu, Shengwei Irvine, Darrell J. Universal redirection of CAR T cells against solid tumours via membrane-inserted ligands for the CAR |
title | Universal redirection of CAR T cells against solid tumours via membrane-inserted ligands for the CAR |
title_full | Universal redirection of CAR T cells against solid tumours via membrane-inserted ligands for the CAR |
title_fullStr | Universal redirection of CAR T cells against solid tumours via membrane-inserted ligands for the CAR |
title_full_unstemmed | Universal redirection of CAR T cells against solid tumours via membrane-inserted ligands for the CAR |
title_short | Universal redirection of CAR T cells against solid tumours via membrane-inserted ligands for the CAR |
title_sort | universal redirection of car t cells against solid tumours via membrane-inserted ligands for the car |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10504084/ https://www.ncbi.nlm.nih.gov/pubmed/37291434 http://dx.doi.org/10.1038/s41551-023-01048-8 |
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