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IL7-Fc Enhances the Efficacy of Adoptive T Cell Therapy under Lymphopenic Conditions in a Murine Melanoma Model

Adoptive cell therapy (ACT) using tumor-reactive T cells is a promising form of immunotherapy to specifically target cancer. However, the survival and functional maintenance of adoptively transferred T cells remains a challenge, ultimately limiting their efficacy. Here, we evaluated the use of recom...

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Autores principales: Yu, Eun M., Cho, Eunjung, Singh, Rohit, Kim, Seon-Hee, Han, Chungyong, Han, Seongeun, Lee, Don G., Kim, Young H., Kwon, Byoung S., Choi, Beom K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392867/
https://www.ncbi.nlm.nih.gov/pubmed/34440787
http://dx.doi.org/10.3390/cells10082018
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author Yu, Eun M.
Cho, Eunjung
Singh, Rohit
Kim, Seon-Hee
Han, Chungyong
Han, Seongeun
Lee, Don G.
Kim, Young H.
Kwon, Byoung S.
Choi, Beom K.
author_facet Yu, Eun M.
Cho, Eunjung
Singh, Rohit
Kim, Seon-Hee
Han, Chungyong
Han, Seongeun
Lee, Don G.
Kim, Young H.
Kwon, Byoung S.
Choi, Beom K.
author_sort Yu, Eun M.
collection PubMed
description Adoptive cell therapy (ACT) using tumor-reactive T cells is a promising form of immunotherapy to specifically target cancer. However, the survival and functional maintenance of adoptively transferred T cells remains a challenge, ultimately limiting their efficacy. Here, we evaluated the use of recombinant IL7-Fc in ACT. In a lymphopenic murine melanoma model, IL7-Fc treatment led to the enhanced inhibition of tumor growth with an increased number of adoptively transferred CD8(+) T cells in tumor tissue and tumor-draining lymph nodes. Additionally, IL7-Fc further enhanced anti-tumor responses that were induced by recombinant human IL2 in the same mouse model. In contrast, in an immunocompetent murine melanoma model, IL7-Fc dampened the anti-tumor immunity. Further, IL7-Fc decreased the proliferation of adoptively transferred and immune-activated tumor-reactive CD8(+) T cells in immunocompetent mice by inducing the massive expansion of endogenous T cells, thereby limiting the space for adoptively transferred T cells. Our data suggest that IL7-Fc is principally beneficial for enhancing the efficacy of tumor-reactive T-cells in lymphopenic conditions for the ACT.
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spelling pubmed-83928672021-08-28 IL7-Fc Enhances the Efficacy of Adoptive T Cell Therapy under Lymphopenic Conditions in a Murine Melanoma Model Yu, Eun M. Cho, Eunjung Singh, Rohit Kim, Seon-Hee Han, Chungyong Han, Seongeun Lee, Don G. Kim, Young H. Kwon, Byoung S. Choi, Beom K. Cells Article Adoptive cell therapy (ACT) using tumor-reactive T cells is a promising form of immunotherapy to specifically target cancer. However, the survival and functional maintenance of adoptively transferred T cells remains a challenge, ultimately limiting their efficacy. Here, we evaluated the use of recombinant IL7-Fc in ACT. In a lymphopenic murine melanoma model, IL7-Fc treatment led to the enhanced inhibition of tumor growth with an increased number of adoptively transferred CD8(+) T cells in tumor tissue and tumor-draining lymph nodes. Additionally, IL7-Fc further enhanced anti-tumor responses that were induced by recombinant human IL2 in the same mouse model. In contrast, in an immunocompetent murine melanoma model, IL7-Fc dampened the anti-tumor immunity. Further, IL7-Fc decreased the proliferation of adoptively transferred and immune-activated tumor-reactive CD8(+) T cells in immunocompetent mice by inducing the massive expansion of endogenous T cells, thereby limiting the space for adoptively transferred T cells. Our data suggest that IL7-Fc is principally beneficial for enhancing the efficacy of tumor-reactive T-cells in lymphopenic conditions for the ACT. MDPI 2021-08-07 /pmc/articles/PMC8392867/ /pubmed/34440787 http://dx.doi.org/10.3390/cells10082018 Text en © 2021 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
Yu, Eun M.
Cho, Eunjung
Singh, Rohit
Kim, Seon-Hee
Han, Chungyong
Han, Seongeun
Lee, Don G.
Kim, Young H.
Kwon, Byoung S.
Choi, Beom K.
IL7-Fc Enhances the Efficacy of Adoptive T Cell Therapy under Lymphopenic Conditions in a Murine Melanoma Model
title IL7-Fc Enhances the Efficacy of Adoptive T Cell Therapy under Lymphopenic Conditions in a Murine Melanoma Model
title_full IL7-Fc Enhances the Efficacy of Adoptive T Cell Therapy under Lymphopenic Conditions in a Murine Melanoma Model
title_fullStr IL7-Fc Enhances the Efficacy of Adoptive T Cell Therapy under Lymphopenic Conditions in a Murine Melanoma Model
title_full_unstemmed IL7-Fc Enhances the Efficacy of Adoptive T Cell Therapy under Lymphopenic Conditions in a Murine Melanoma Model
title_short IL7-Fc Enhances the Efficacy of Adoptive T Cell Therapy under Lymphopenic Conditions in a Murine Melanoma Model
title_sort il7-fc enhances the efficacy of adoptive t cell therapy under lymphopenic conditions in a murine melanoma model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392867/
https://www.ncbi.nlm.nih.gov/pubmed/34440787
http://dx.doi.org/10.3390/cells10082018
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