Ex vivo expansion of tumor specific lymphocytes with IL-15 and IL-21 for adoptive immunotherapy in melanoma
Eduardo Huartea, Jan Fishera, Mary Jo Turkb, Diane Mellingera, Cathy Fostera, Benita Wolfc, Kenneth R. Meehana, Camilo E. Fadula, Marc S. Ernstoff
Cancer Letters Volume 285, Issue 1, 18 November 2009, Pages 80-88
Although T Central Memory cells have been described as the most effective T-cell subtype against tumor growth, little is known about the requirements needed for their optimal ex vivo generation.
Hence, our goal is to establish a protocol that will lead to consistent ex vivo generation of lymphocytes skewed toward a Central Memory phenotype. Antigen-specific T-cell lines were generated by ex vivo stimulation with Class-I and Class-II melanoma peptide pulsed Dendritic Cells in the presence of either IL-2 or IL-15 plus IL-21. Tumor specific lymphocytes of both Central Memory and effector characteristics were consistently generated from healthy donors and melanoma patients.
IL15/IL21 cultures result in a cell population with a lower proportion of CD4+CD25highFoxP3+ regulatory cells and higher number of CD8+ and CD56+ cells, and consequently render a higher yield of cells with a greater cytolytic activity and IFN-γ production against melanoma cell lines.