A comparative analysis of tumor immunity induced by peptide or cell-based vaccination

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Cell based vaccine strategies are capable of inducing cytotoxic T-cell responses, but it is less clear whether such strategies induce significant humoral immunity against “tumor-specific” antigens (TSA). Using a novel vaccine strategy that combines the synergistic action of CpG oligodeoxynucleotides (ODN) and GM-CSF, we compared humoral and cellular immune responses between mice vaccinated with either purified peptide vs. mice vaccinated with irradiated whole tumor cells as the antigen source. The murine 38C13 lymphoma model was used in which the idiotype (Id) of 38C13 surface IgM serves as the TSA. Syngeneic C3H/HeN mice received 3 weekly intra-peritoneal vaccinations with GM-CSF-secreting bystander cells and CpG 1826 (100ug) admixed with either Id peptide (40ug) or irradiated 38C13 lymphoma cells (1X10⁶ cells). Serum was obtained weekly after each vaccination and splenocytes were harvested after the third vaccine. Anti-idiotype titers and IFN-γ secretion from splenocytes incubated with irradiated tumor cells or purified Id peptide were quantified by ELISA. Both peptide and cell based vaccines were capable of inducing anti-idiotype antibody responses in the serum. Multiple vaccinations produced a “booster effect” on antibody titers in both peptide and cell based vaccines. Similarly, IFN-γ secretion appeared comparable between the two strategies, in which splenocytes from either group were also cross-reactive to both purified peptide or irradiated tumor cells. In conclusion, our vaccine strategy utilizing whole cells as a vehicle for antigen delivery combined with CpG ODN and GM-CSF, induced tumor specific immunity in this lymphoma model. Such whole cell-based vaccine strategies negate the need for identifying TSA for tumor therapy. Furthermore, immunity induced by whole tumor cells is potentially directed at multiple antigens, reducing the risk for clonal escape.