Vaccination with tumor peptide in CpG adjuvant protects via IFN-gamma-dependent CD4 cell immunity

The low frequency of tumor Ag-specific T cells in vivo has made it challenging to directly measure their clonal sizes and cytokine signatures. We used a new generation ELISPOT approach to study the constitutive immunogenicity of the RMA tumor in syngeneic B6 mice and adjuvant-guided immunity against an MHC class II-restricted RMA peptide, H11.1. The RMA tumor was found to activate cells of the innate immune system and to induce a type 1 polarized, RMA-specific CD4 and CD8 T cell response. With clonal sizes approximately 10/10(6), the magnitude of this constitutively induced immune response did not suffice to control the tumor cell growth. In contrast, immunization with H11.1 peptide, using an immunostimulatory CpG oligonucleotide or CFA as adjuvant, engaged approximately 25- or approximately 10-fold higher clonal sizes of type 1 polarized CD4 cells, respectively. Therefore, the CpG oligonucleotide functioned as a stronger type 1 adjuvant and, unlike CFA, elicited protective immunity. The protection was IFN-gamma dependent, as it was not inducible in IFN-gamma knockout mice. Therefore, CpG adjuvant-guided induction of type 1 immunity against tumor Ags might be a promising subunit vaccination approach.