Cancer vaccine design: A novel bacterial adjuvant for peptide-specific CTLinduction

The recent identification of tumor Ags as potential vaccines has prompted t he search for efficient adjuvants and delivery systems, especially in the c ase of peptide-based vaccination protocols. Here, we investigated the adjuv ant potential of the recombinant 40-kDa outer membrane protein of Klebselli a pneumoniae (P40) for specific CTL induction. We studied the CTL response induced in HLA-A*0201/K-b transgenic mice immunized with peptides derived f rom two melanoma-associated differentiation Ags, the HLA-A*0201-restricted decapeptide Melan-A(26-35) substituted at position 2 and the K-b-restricted tyrosinase-related protein 2(181-188) T cell epitope. We found that both p eptides are able to generate a specific CTL response when mixed with the pr otein in the absence of conventional adjuvant. This CTL response is a funct ion of the amount of P40 used for immunization. Moreover, the CTI, response generated against the tyrosinase-related protein 2(181-188) peptide in pre sence of P40 is associated with tumor protection in two different experimen tal models and is independent of the presence of CD4(+) T lymphocytes. Thus , the recombinant bacterial protein P40 functions as a potent immunological adjuvant for specific CTL induction.