Cancer Vaccine Design: A Novel Bacterial Adjuvant for Peptide-Specific CTL Induction

• Published in: The Journal of immunology (1950) 2001-04, Vol.166 (7), p.4612-4619
• Main Authors: Miconnet, Isabelle, Coste, Isabelle, Beermann, Friedrich, Haeuw, Jean-Francois, Cerottini, Jean-Charles, Bonnefoy, Jean-Yves, Romero, Pedro, Renno, Toufic
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - chemical synthesis; Animals; Antigens, Neoplasm - administration & dosage; Antigens, Neoplasm - immunology; Bacterial Outer Membrane Proteins - administration & dosage; Bacterial Outer Membrane Proteins - immunology; cancer vaccines; Cancer Vaccines - administration & dosage; Cancer Vaccines - chemical synthesis; Cancer Vaccines - immunology; CD8-Positive T-Lymphocytes - immunology; Cytotoxicity, Immunologic - immunology; Drug Combinations; Epitopes, T-Lymphocyte - immunology; Immunotherapy, Active - methods; Injections, Subcutaneous; Intramolecular Oxidoreductases - administration & dosage; Intramolecular Oxidoreductases - immunology; Klebsiella pneumoniae - immunology; Lymphocyte Depletion; Macromolecular Substances; MART-1 Antigen; Melanoma, Experimental - immunology; Melanoma, Experimental - pathology; Melanoma, Experimental - prevention & control; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Neoplasm Proteins - administration & dosage; Neoplasm Proteins - immunology; Neoplasm Transplantation; P40 protein; Peptide Fragments - administration & dosage; Peptide Fragments - chemical synthesis; Peptide Fragments - immunology; T-Lymphocytes, Cytotoxic - immunology; Titrimetry; Tumor Cells, Cultured - transplantation
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.7.4612

The recent identification of tumor Ags as potential vaccines has prompted the search for efficient adjuvants and delivery systems, especially in the case of peptide-based vaccination protocols. Here, we investigated the adjuvant potential of the recombinant 40-kDa outer membrane protein of Klebsiella pneumoniae (P40) for specific CTL induction. We studied the CTL response induced in HLA-A*0201/K(b) transgenic mice immunized with peptides derived from 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 peptides are able to generate a specific CTL response when mixed with the protein in the absence of conventional adjuvant. This CTL response is a function of the amount of P40 used for immunization. Moreover, the CTL response generated against the tyrosinase-related protein 2(181-188) peptide in presence of P40 is associated with tumor protection in two different experimental 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.