%0 Journal Article
%T Comparison of na£¿ve and central memory derived CD8+ effector cell engraftment fitness and function following adoptive transfer
%A Armen Mardiros
%A Brenda Aguilar
%A Carolina Berger
%A ChingLam W. Wong
%A Christine E. Brown
%A Ellie Taus
%A Lihua E. Budde
%A Michael C. Jensen
%A Ryan Urak
%A Stephen J. Forman
%A Wen-Chung Chang
%A Xiuli Wang
%J Archive of "Oncoimmunology".
%D 2016
%R 10.1080/2162402X.2015.1072671
%X Human CD8+ effector T cells derived from CD45RO+CD62L+ precursors enriched for central memory (TCM) precursors retain the capacity to engraft and reconstitute functional memory upon adoptive transfer, whereas effectors derived from CD45RO+CD62L£¿ precursors enriched for effector memory precursors do not. Here we sought to compare the engraftment fitness and function of CD8+ effector T cells derived from CD45RA+CD62L+ precursors enriched for na£¿ve and stem cell memory precursors (TN/SCM) with that of TCM. We found that cytotoxic T cells (CTLs) derived from TCM transcribed higher levels of CD28, FOS, INF¦Ã, Eomesodermin (Eomes), and lower levels of BCL2L11, maintained higher levels of phosphorylated AKT, and displayed enhanced sensitivity to the proliferative and anti-apoptotic effects of ¦Ã-chain cytokines compared to CTLs derived from TN/SCM. Higher frequencies of CTLs derived from TCM retained CD28 expression and upon activation secreted higher levels of IL-2. In NOD/Scid IL-2R¦ÃCnull mice, CD8+ TCM derived CTLs engrafted to higher frequencies in response to human IL-15 and mounted robust proliferative responses to an immunostimulatory vaccine. Similarly, CD8+ TCM derived CD19CAR+ CTLs exhibited superior antitumor potency following adoptive transfer compared to their CD8+ TN/SCM derived counterparts. These studies support the use of TCM enriched cell products for adoptive therapy of cancer
%K Antitumor activity
%K adoptive therapy
%K central memory T cell derived CTLs
%K engraftment fitness
%K na£¿ve T cell derived CTLs
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4760301/