Rapid accumulation of adoptively transferred CD8+ T cells at the tumor site is associated with long-term control of SV40 T antigen-induced tumors

We previously established a model to study CD8(+) T cell (T-CD8)-based adoptive immunotherapy of cancer using line SV11 mice that develop choroid plexus tumors in the brain due to transgenic expression of Simian Virus 40 large T antigen (Tag). These mice are tolerant to the three dominant T-CD8-recognized Tag epitopes I, II/III and IV. However, adoptive transfer of spleen cells from naive C57BL/6 (B6) mice prolongs SV11 survival following T-CD8 priming against the endogenous Tag epitope IV. In addition, survival of SV11 mice is dramatically increased following transfer of lymphocytes from Tag-immune B6 mice. In the current study, we compared the kinetics and magnitude of Tag-specific T-CD8 accumulation at the tumor site following adoptive transfer with a high dose of either Tag-immune or naive donor cells or decreasing doses of Tag-immune lymphocytes. Following adoptive transfer of Tag-immune cells, epitope I- and IV-specific T-CD8 accumulated to high levels in the brain of SV11 mice, peaking at 5-7 days, while epitope IV-specific T-CD8 derived from naive donors required three weeks to achieve peak levels. A similar delay in the peak of epitope IV-specific T-CD8 accumulation was observed when tenfold fewer Tag-immune donor cells were administered, reducing control of tumor progression. These results suggest that efficient and prolonged control of established autochthonous tumors is associated with high-level early accumulation of adoptively transferred T cells. We also provide evidence that although multiple specificities are represented in the Tag immune donor lymphocytes, epitope IV-specific donor T-CD8 play a predominant role in control of tumor growth.