Expansion and characterization of human melanoma tumor-infiltrating lymphocytes (TILs).

<h4>Background</h4>Various immunotherapeutic strategies for cancer are aimed at augmenting the T cell response against tumor cells. Adoptive cell therapy (ACT), where T cells are manipulated ex vivo and subsequently re-infused in an autologous manner, has been performed using T cells fro...

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Autores principales: Linh T Nguyen, Pei Hua Yen, Jessica Nie, Nicole Liadis, Danny Ghazarian, Ayman Al-Habeeb, Alexandra Easson, Wey Leong, Joan Lipa, David McCready, Michael Reedijk, David Hogg, Anthony M Joshua, Ian Quirt, Hans Messner, Patricia Shaw, Michael Crump, Eran Sharon, Pamela S Ohashi
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2010
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Acceso en línea:https://doaj.org/article/fd7e427dc12b40768de11d9f16cd9cac
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Sumario:<h4>Background</h4>Various immunotherapeutic strategies for cancer are aimed at augmenting the T cell response against tumor cells. Adoptive cell therapy (ACT), where T cells are manipulated ex vivo and subsequently re-infused in an autologous manner, has been performed using T cells from various sources. Some of the highest clinical response rates for metastatic melanoma have been reported in trials using tumor-infiltrating lymphocytes (TILs). These protocols still have room for improvement and furthermore are currently only performed at a limited number of institutions. The goal of this work was to develop TILs as a therapeutic product at our institution.<h4>Principal findings</h4>TILs from 40 melanoma tissue specimens were expanded and characterized. Under optimized culture conditions, 72% of specimens yielded rapidly proliferating TILs as defined as at least one culture reaching ≥3×10(7) TILs within 4 weeks. Flow cytometric analyses showed that cultures were predominantly CD3+ T cells, with highly variable CD4+:CD8+ T cell ratios. In total, 148 independent bulk TIL cultures were assayed for tumor reactivity. Thirty-four percent (50/148) exhibited tumor reactivity based on IFN-γ production and/or cytotoxic activity. Thirteen percent (19/148) showed specific cytotoxic activity but not IFN-γ production and only 1% (2/148) showed specific IFN-γ production but not cytotoxic activity. Further expansion of TILs using a 14-day "rapid expansion protocol" (REP) is required to induce a 500- to 2000-fold expansion of TILs in order to generate sufficient numbers of cells for current ACT protocols. Thirty-eight consecutive test REPs were performed with an average 1865-fold expansion (+/- 1034-fold) after 14 days.<h4>Conclusions</h4>TILs generally expanded efficiently and tumor reactivity could be detected in vitro. These preclinical data from melanoma TILs lay the groundwork for clinical trials of ACT.