Adoptive cell therapy provides an attractive treatment of cancer, and our expanding capacity to target tumor antigens is driven by genetically engineered human T lymphocytes that express genes encoding tumor-specific T cell receptors (TCRs). The intrinsic properties of cultured T cells used for therapy were reported to have tremendous influences on their persistence and antitumor efficacy in vivo. In this study, we isolated CD8(+) central memory T cells from peripheral blood lymphocytes of healthy donors, and then transferred with the gene encoding TCR specific for tumor antigen using recombinant adenovirus vector Ad5F35-TRAV-TRBV. We found effector T cells derived from central memory T cells improved cell viability, maintained certain level of CD62L expression, and reacquired the CD62L(+)CD44(high) phenotype of central memory T cells after effector T cells differentiation. We then compared the antitumor reactivity of central memory T cells and CD8(+)T cells after TCR gene transferred. The results indicated that tumor-specific TCR gene being transferred to central memory T cells effectively increased the specific killing of antigen positive tumor cells and the expression of cytolytic granule protein. Furthermore, TCR gene transferred central memory T cells were more effective than TCR gene transferred CD8(+)T cells in CTL activity and effector cytokine secretion. These results implicated that isolating central memory T cells rather than CD8(+)T cells for insertion of gene encoding tumor-specific TCR may provide a superior tumor-reactive T cell population for adoptive transfer.
Keywords: AFP; CAR; CD8(+)T cell; CTL; Calcein-AM; IFN-γ; IL-2; Immunotherapy; LNs; T cell receptor; T(CM); T(EM); TCR; TE; TIL; TM; TN; Transfer; alpha-fetoprotein; calcein–acetoxymethyl ester; central memory T cell; coxsackie/adenovirus receptors; cytotoxic lymphocytes; effector T cell; effector memory T cell; interferon-gamma; interlukin-2; lymph nodes; mAb; memory T cell; monoclonal antibody; naïve T cell; tumor-infiltrating lymphocyte.
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