Journal Article

Adoptively transferred effector cells derived from naoe¯ve rather than central memory CD8 super(+) T cells mediate superior antitumor immunity

Borman, Zachary A, Muranski, Pawel, Palmer, Douglas C, Leonard, Warren J, Logun, Carol, Danner, Robert L, Sanchez-Perez, Luis, Ji, Yun, Reger, Robert N, Hinrichs, Christian S, Gattinoni, Luca, Yu, Zhiya, Cassard, Lydie, Kern, Steven J, Restifo, Nicholas P, Spolski, Rosanne, Rosenberg, Steven A

2009

Overview

Effector cells derived from central memory CD8 super(+) T cells were reported to engraft and survive better than those derived from effector memory populations, suggesting thatthey are superior for use in adoptive immunotherapy studies. However, previous studies did not evaluate the relative efficacyof effector cells derived from naoe¯ve T cells. We sought to investigate the efficacy of tumor-specific effector cells derivedfrom naoe¯ve or central memory T-cell subsets using transgenic or retrovirally transduced T cells engineered to express a tumor-specificT-cell receptor. We found that naoe¯ve, rather than central memory T cells, gave rise to an effector population that mediatedsuperior antitumor immunity upon adoptive transfer. Effector cells developed from naoe¯ve T cells lost the expression of CD62Lmore rapidly than those derived from central memory T cells, but did not acquire the expression of KLRG-1, a marker for terminaldifferentiation and replicative senescence. Consistent with this KLRG-1 super(-) phenotype, naoe¯ve-derived cells were capable of a greater proliferative burst and had enhanced cytokine production after adoptivetransfer. These results indicate that insertion of genes that confer antitumor specificity into naoe¯ve rather than centralmemory CD8 super(+) T cells may allow superior efficacy upon adoptive transfer.