Clinical Scale Central Memory T Cell Enrichment for Adoptive T Cell Therapy

Abstract 5180

The adoptive transfer of genetically engineered lymphocytes is a promising strategy to treat cancer. However, the efficacy of adoptive immunotherapy in humans is often limited and the critical parameters for the in vivo efficacy remain poorly defined. One aspect may be the limited survival time and self renewal capacity of transferred T cells in vivo.

Antigen-experienced memory T cells (TM) can be divided further into central memory (TCM) and effector memory (TEM) subsets. CD8+ TEM lack CCR7/CD62L, migrate preferentially to peripheral tissues, and exhibit immediate effector function, whereas CD8+ TCM express CD62L and CCR7, which promote migration into LNs. TCM proliferate rapidly if re-exposed to antigen and there is evidence that T cell lines derived from TCM have increased persistence and functionality in vivo. Thus TCM might be a superior starting population for T cell therapy using transduced T cells.

We have developed a GMP compatible sorting strategy for TCM allowing their selective transduction and large-scale expansion. TCM cell were isolated by a sequential depletion of CD45RA+ and CD4+ and subsequent enrichment of CD62L+ cells using the CliniMACS® Plus Instrument. CD8+ TCM from peripheral blood of cancer patients were obtained in large numbers from leukapheresis products and genetically engineered with tumor-specific TCRs. After expansion in vitro to numbers sufficient for patient treatment the TCM population retained high CD62L expression. This protocol can be the basis for clinical studies on the efficiency of TCM derived T cell lines in T cell therapy against tumors.