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Addition of Interleukin-21 for Expansion of T-Cells for Adoptive Immunotherapy of Murine Melanoma

We previously demonstrated that interleukin (IL)-7/15 was superior to IL-2 for expansion of T cells in vitro for adoptive immunotherapy. We sought to ascertain whether IL-21 would further improve yield and therapeutic efficacy of T cells in culture. Naïve T cell receptor (TcR) transgenic splenocytes...

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Autores principales: Zoon, Christine Kathryn, Wan, Wen, Graham, Laura, Bear, Harry D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425106/
https://www.ncbi.nlm.nih.gov/pubmed/25903148
http://dx.doi.org/10.3390/ijms16048744
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author Zoon, Christine Kathryn
Wan, Wen
Graham, Laura
Bear, Harry D.
author_facet Zoon, Christine Kathryn
Wan, Wen
Graham, Laura
Bear, Harry D.
author_sort Zoon, Christine Kathryn
collection PubMed
description We previously demonstrated that interleukin (IL)-7/15 was superior to IL-2 for expansion of T cells in vitro for adoptive immunotherapy. We sought to ascertain whether IL-21 would further improve yield and therapeutic efficacy of T cells in culture. Naïve T cell receptor (TcR) transgenic splenocytes or antigen-sensitized lymph node cells were harvested from PMEL-1 mice and exposed to bryostatin-1 and ionomycin (B/I) for 18 h. Cells were then cultured in IL-2, IL-21, IL-7/15 or IL-7/15/21 for six days. Harvested cells were analyzed by flow cytometry and used to treat C57Bl/6 mice injected intravenously with B16 melanoma. Lungs were harvested and metastases counted 14 days after treatment. Culturing lymphocytes in IL-7/15/21 increased expansion compared to IL-2 or IL-7/15. IL-21 and IL-7/15/21 increased CD8+ cells compared to IL-2 or IL-7/15. IL-21 preferentially expanded a CD8+CD44−CD62L+ T “naïve” population, whereas IL-7/15/21 increased CD8+CD44+CD62Lhigh central-memory T cells. T cells grown in IL-7/15/21 were more effective at reducing metastases than IL-2. The addition of IL-21 to IL-7/15 induced greater expansion of lymphocytes in culture and increased the yield of CD8+ T central-memory cells vs. IL-7/15 alone. This may have significant impact on future clinical trials of adoptive immunotherapy, particularly for generating adequate numbers of lymphocytes for treatment.
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spelling pubmed-44251062015-05-20 Addition of Interleukin-21 for Expansion of T-Cells for Adoptive Immunotherapy of Murine Melanoma Zoon, Christine Kathryn Wan, Wen Graham, Laura Bear, Harry D. Int J Mol Sci Article We previously demonstrated that interleukin (IL)-7/15 was superior to IL-2 for expansion of T cells in vitro for adoptive immunotherapy. We sought to ascertain whether IL-21 would further improve yield and therapeutic efficacy of T cells in culture. Naïve T cell receptor (TcR) transgenic splenocytes or antigen-sensitized lymph node cells were harvested from PMEL-1 mice and exposed to bryostatin-1 and ionomycin (B/I) for 18 h. Cells were then cultured in IL-2, IL-21, IL-7/15 or IL-7/15/21 for six days. Harvested cells were analyzed by flow cytometry and used to treat C57Bl/6 mice injected intravenously with B16 melanoma. Lungs were harvested and metastases counted 14 days after treatment. Culturing lymphocytes in IL-7/15/21 increased expansion compared to IL-2 or IL-7/15. IL-21 and IL-7/15/21 increased CD8+ cells compared to IL-2 or IL-7/15. IL-21 preferentially expanded a CD8+CD44−CD62L+ T “naïve” population, whereas IL-7/15/21 increased CD8+CD44+CD62Lhigh central-memory T cells. T cells grown in IL-7/15/21 were more effective at reducing metastases than IL-2. The addition of IL-21 to IL-7/15 induced greater expansion of lymphocytes in culture and increased the yield of CD8+ T central-memory cells vs. IL-7/15 alone. This may have significant impact on future clinical trials of adoptive immunotherapy, particularly for generating adequate numbers of lymphocytes for treatment. MDPI 2015-04-20 /pmc/articles/PMC4425106/ /pubmed/25903148 http://dx.doi.org/10.3390/ijms16048744 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zoon, Christine Kathryn
Wan, Wen
Graham, Laura
Bear, Harry D.
Addition of Interleukin-21 for Expansion of T-Cells for Adoptive Immunotherapy of Murine Melanoma
title Addition of Interleukin-21 for Expansion of T-Cells for Adoptive Immunotherapy of Murine Melanoma
title_full Addition of Interleukin-21 for Expansion of T-Cells for Adoptive Immunotherapy of Murine Melanoma
title_fullStr Addition of Interleukin-21 for Expansion of T-Cells for Adoptive Immunotherapy of Murine Melanoma
title_full_unstemmed Addition of Interleukin-21 for Expansion of T-Cells for Adoptive Immunotherapy of Murine Melanoma
title_short Addition of Interleukin-21 for Expansion of T-Cells for Adoptive Immunotherapy of Murine Melanoma
title_sort addition of interleukin-21 for expansion of t-cells for adoptive immunotherapy of murine melanoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4425106/
https://www.ncbi.nlm.nih.gov/pubmed/25903148
http://dx.doi.org/10.3390/ijms16048744
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