Huarte, EduardoFisher, JanTurk, Mary JoMellinger, DianeFoster, CathyWolf, BenitaMeehan, Kenneth R.Fadul, Camilo E.Ernstoff, Marc S.2012-10-292012-10-292012-10-29200910.1016/j.canlet.2009.05.003https://infoscience.epfl.ch/handle/20.500.14299/86382Although 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(+)CD25(high)FoxP3(+) 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-gamma production against melanoma cell lines.Cell ProliferationImmunologic MemoryImmunotherapyAdoptiveEx vivo expansion of tumor specific lymphocytes with IL-15 and IL-21 for adoptive immunotherapy in melanomatext::journal::journal article::research article