Comparison of naïve and central memory derived CD8 effector cell engraftment fitness and function following adoptive transfer.

Human CD8 effector T cells derived from CD45ROCD62L precursors enriched for central memory (T) precursors retain the capacity to engraft and reconstitute functional memory upon adoptive transfer, whereas effectors derived from CD45ROCD62L 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 CD45RACD62L precursors enriched for naïve and stem cell memory precursors (T) with that of T. We found that cytotoxic T cells (CTLs) derived from T transcribed higher levels of CD28, FOS, INFγ, 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 γ-chain cytokines compared to CTLs derived from T. Higher frequencies of CTLs derived from T retained CD28 expression and upon activation secreted higher levels of IL-2. In NOD/ IL-2RγC mice, CD8 T derived CTLs engrafted to higher frequencies in response to human IL-15 and mounted robust proliferative responses to an immunostimulatory vaccine. Similarly, CD8 T derived CD19CAR CTLs exhibited superior antitumor potency following adoptive transfer compared to their CD8 T derived counterparts. These studies support the use of T enriched cell products for adoptive therapy of cancer.