Different alpha fetoprotein epitope-specific CD8 T cells possess distinct antitumor function (VAC13P.1130)

Using lentivector (lv) immunization and epitope-optimization, we have recently identified three CD8 epitopes in the hepatocellular carcinoma (HCC) associated antigen of murine alpha fetoprotein (AFP) that could effectively activate CD8 T cells in mice, resulting in potent antitumor effect that can completely prevent mice from tumor challenge and prevent carcinogen-induce autochthonous HCC. In this report, we studied whether the epitope-specific CD8 responses can be further enhanced by peptide boost and investigate if the newly identified epitope specific T cells can kill AFP+ tumor cells and have equal antitumor activity. We found that the lv-primed AFP-specific CD8 responses can be boosted by AFP peptides even at the peak of primary responses. As much as 20 folds increase of AFP-specific CD8 responses can be achieved by peptide boost. However, the kinetics and the antitumor effect of different epitope-specific CD8 responses are drastically different. While the epitope AFP 499 -specific CD8 T cells possess potent CTL activity against AFP+ tumor cells and generate strong antitumor effect in vivo, the AFP 212 -specific CD8 T cells have a very limited CTL activity and antitumor effect though they can produce high level of IFNg. The mechanisms underpinning the functional differences will be reported. This finding demonstrates that cancer vaccines must be able to elicit tumor-killing immune effector cells in order to generate antitumor effect.