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A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity
Chimeric antigen receptor (CAR) T cell therapy is routinely used to treat patients with refractory hematologic malignancies. However, a significant proportion of patients experience suboptimal CAR T cell cytotoxicity and persistence that can permit tumor cell escape and disease relapse. Here we show...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9192727/ https://www.ncbi.nlm.nih.gov/pubmed/35697686 http://dx.doi.org/10.1038/s41467-022-30860-0 |
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author | Kim, Miriam Y. Jayasinghe, Reyka Devenport, Jessica M. Ritchey, Julie K. Rettig, Michael P. O’Neal, Julie Staser, Karl W. Kennerly, Krista M. Carter, Alun J. Gao, Feng Lee, Byung Ha Cooper, Matthew L. DiPersio, John F. |
author_facet | Kim, Miriam Y. Jayasinghe, Reyka Devenport, Jessica M. Ritchey, Julie K. Rettig, Michael P. O’Neal, Julie Staser, Karl W. Kennerly, Krista M. Carter, Alun J. Gao, Feng Lee, Byung Ha Cooper, Matthew L. DiPersio, John F. |
author_sort | Kim, Miriam Y. |
collection | PubMed |
description | Chimeric antigen receptor (CAR) T cell therapy is routinely used to treat patients with refractory hematologic malignancies. However, a significant proportion of patients experience suboptimal CAR T cell cytotoxicity and persistence that can permit tumor cell escape and disease relapse. Here we show that a prototype pro-lymphoid growth factor is able to enhance CAR T cell efficacy. We demonstrate that a long-acting form of recombinant human interleukin-7 (IL-7) fused with hybrid Fc (rhIL-7-hyFc) promotes proliferation, persistence and cytotoxicity of human CAR T cells in xenogeneic mouse models, and murine CAR T cells in syngeneic mouse models, resulting in long-term tumor-free survival. Thus, rhIL-7-hyFc represents a tunable clinic-ready adjuvant for improving suboptimal CAR T cell activity. |
format | Online Article Text |
id | pubmed-9192727 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-91927272022-06-15 A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity Kim, Miriam Y. Jayasinghe, Reyka Devenport, Jessica M. Ritchey, Julie K. Rettig, Michael P. O’Neal, Julie Staser, Karl W. Kennerly, Krista M. Carter, Alun J. Gao, Feng Lee, Byung Ha Cooper, Matthew L. DiPersio, John F. Nat Commun Article Chimeric antigen receptor (CAR) T cell therapy is routinely used to treat patients with refractory hematologic malignancies. However, a significant proportion of patients experience suboptimal CAR T cell cytotoxicity and persistence that can permit tumor cell escape and disease relapse. Here we show that a prototype pro-lymphoid growth factor is able to enhance CAR T cell efficacy. We demonstrate that a long-acting form of recombinant human interleukin-7 (IL-7) fused with hybrid Fc (rhIL-7-hyFc) promotes proliferation, persistence and cytotoxicity of human CAR T cells in xenogeneic mouse models, and murine CAR T cells in syngeneic mouse models, resulting in long-term tumor-free survival. Thus, rhIL-7-hyFc represents a tunable clinic-ready adjuvant for improving suboptimal CAR T cell activity. Nature Publishing Group UK 2022-06-13 /pmc/articles/PMC9192727/ /pubmed/35697686 http://dx.doi.org/10.1038/s41467-022-30860-0 Text en © The Author(s) 2022 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 Kim, Miriam Y. Jayasinghe, Reyka Devenport, Jessica M. Ritchey, Julie K. Rettig, Michael P. O’Neal, Julie Staser, Karl W. Kennerly, Krista M. Carter, Alun J. Gao, Feng Lee, Byung Ha Cooper, Matthew L. DiPersio, John F. A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity |
title | A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity |
title_full | A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity |
title_fullStr | A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity |
title_full_unstemmed | A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity |
title_short | A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity |
title_sort | long-acting interleukin-7, rhil-7-hyfc, enhances car t cell expansion, persistence, and anti-tumor activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9192727/ https://www.ncbi.nlm.nih.gov/pubmed/35697686 http://dx.doi.org/10.1038/s41467-022-30860-0 |
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