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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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.
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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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