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Efficient lentiviral transduction method to gene modify cord blood CD8(+) T cells for cancer therapy applications
Adoptive T cell therapy utilizing tumor-specific autologous T cells has shown promising results for cancer treatment. However, the limited numbers of autologous tumor-associated antigen (TAA)-specific T cells and the functional aberrancies, due to disease progression or treatment, remain factors tha...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056177/ https://www.ncbi.nlm.nih.gov/pubmed/33898633 http://dx.doi.org/10.1016/j.omtm.2021.03.015 |
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author | Lo Presti, Vania Cornel, Annelisa M. Plantinga, Maud Dünnebach, Ester Kuball, Jurgen Boelens, Jaap Jan Nierkens, Stefan van Til, Niek P. |
author_facet | Lo Presti, Vania Cornel, Annelisa M. Plantinga, Maud Dünnebach, Ester Kuball, Jurgen Boelens, Jaap Jan Nierkens, Stefan van Til, Niek P. |
author_sort | Lo Presti, Vania |
collection | PubMed |
description | Adoptive T cell therapy utilizing tumor-specific autologous T cells has shown promising results for cancer treatment. However, the limited numbers of autologous tumor-associated antigen (TAA)-specific T cells and the functional aberrancies, due to disease progression or treatment, remain factors that may significantly limit the success of the therapy. The use of allogeneic T cells, such as umbilical cord blood (CB) derived, overcomes these issues but requires gene modification to induce a robust and specific anti-tumor effect. CB T cells are readily available in CB banks and show low toxicity, high proliferation rates, and increased anti-leukemic effect upon transfer. However, the combination of anti-tumor gene modification and preservation of advantageous immunological traits of CB T cells represent major challenges for the harmonized production of T cell therapy products. In this manuscript, we optimized a protocol for expansion and lentiviral vector (LV) transduction of CB CD8(+) T cells, achieving a transduction efficiency up to 83%. Timing of LV treatment, selection of culture media, and the use of different promoters were optimized in the transduction protocol. LentiBOOST was confirmed as a non-toxic transduction enhancer of CB CD8(+) T cells, with minor effects on the proliferation capacity and cell viability of the T cells. Positively, the use of LentiBOOST does not affect the functionality of the cells, in the context of tumor cell recognition. Finally, CB CD8(+) T cells were more amenable to LV transduction than peripheral blood (PB) CD8+ T cells and maintained a more naive phenotype. In conclusion, we show an efficient method to genetically modify CB CD8(+) T cells using LV, which is especially useful for off-the-shelf adoptive cell therapy products for cancer treatment. |
format | Online Article Text |
id | pubmed-8056177 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-80561772021-04-23 Efficient lentiviral transduction method to gene modify cord blood CD8(+) T cells for cancer therapy applications Lo Presti, Vania Cornel, Annelisa M. Plantinga, Maud Dünnebach, Ester Kuball, Jurgen Boelens, Jaap Jan Nierkens, Stefan van Til, Niek P. Mol Ther Methods Clin Dev Original Article Adoptive T cell therapy utilizing tumor-specific autologous T cells has shown promising results for cancer treatment. However, the limited numbers of autologous tumor-associated antigen (TAA)-specific T cells and the functional aberrancies, due to disease progression or treatment, remain factors that may significantly limit the success of the therapy. The use of allogeneic T cells, such as umbilical cord blood (CB) derived, overcomes these issues but requires gene modification to induce a robust and specific anti-tumor effect. CB T cells are readily available in CB banks and show low toxicity, high proliferation rates, and increased anti-leukemic effect upon transfer. However, the combination of anti-tumor gene modification and preservation of advantageous immunological traits of CB T cells represent major challenges for the harmonized production of T cell therapy products. In this manuscript, we optimized a protocol for expansion and lentiviral vector (LV) transduction of CB CD8(+) T cells, achieving a transduction efficiency up to 83%. Timing of LV treatment, selection of culture media, and the use of different promoters were optimized in the transduction protocol. LentiBOOST was confirmed as a non-toxic transduction enhancer of CB CD8(+) T cells, with minor effects on the proliferation capacity and cell viability of the T cells. Positively, the use of LentiBOOST does not affect the functionality of the cells, in the context of tumor cell recognition. Finally, CB CD8(+) T cells were more amenable to LV transduction than peripheral blood (PB) CD8+ T cells and maintained a more naive phenotype. In conclusion, we show an efficient method to genetically modify CB CD8(+) T cells using LV, which is especially useful for off-the-shelf adoptive cell therapy products for cancer treatment. American Society of Gene & Cell Therapy 2021-03-23 /pmc/articles/PMC8056177/ /pubmed/33898633 http://dx.doi.org/10.1016/j.omtm.2021.03.015 Text en © 2021 The Authors. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Lo Presti, Vania Cornel, Annelisa M. Plantinga, Maud Dünnebach, Ester Kuball, Jurgen Boelens, Jaap Jan Nierkens, Stefan van Til, Niek P. Efficient lentiviral transduction method to gene modify cord blood CD8(+) T cells for cancer therapy applications |
title | Efficient lentiviral transduction method to gene modify cord blood CD8(+) T cells for cancer therapy applications |
title_full | Efficient lentiviral transduction method to gene modify cord blood CD8(+) T cells for cancer therapy applications |
title_fullStr | Efficient lentiviral transduction method to gene modify cord blood CD8(+) T cells for cancer therapy applications |
title_full_unstemmed | Efficient lentiviral transduction method to gene modify cord blood CD8(+) T cells for cancer therapy applications |
title_short | Efficient lentiviral transduction method to gene modify cord blood CD8(+) T cells for cancer therapy applications |
title_sort | efficient lentiviral transduction method to gene modify cord blood cd8(+) t cells for cancer therapy applications |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056177/ https://www.ncbi.nlm.nih.gov/pubmed/33898633 http://dx.doi.org/10.1016/j.omtm.2021.03.015 |
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