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Cancer vaccine design: a novel bacterial adjuvant for peptide-specific CTL induction
Journal of Immunology
Date de publication
Journal Article --- Old month value: Apr 1
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.
Adjuvants, Immunologic/*administration & dosage/chemical synthesis Animals Antigens, Neoplasm/administration & dosage/immunology Bacterial Outer Membrane Proteins/administration & dosage/*immunology CD8-Positive T-Lymphocytes/immunology Cancer Vaccines/administration & dosage/*chemical synthesis/immunology Cytotoxicity, Immunologic/*immunology Drug Combinations Epitopes, T-Lymphocyte/*immunology Immunotherapy, Active/methods Injections, Subcutaneous Intramolecular Oxidoreductases/administration & dosage/immunology Klebsiella pneumoniae/*immunology Lymphocyte Depletion Macromolecular Substances Melanoma, Experimental/immunology/pathology/prevention & control Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Transgenic Neoplasm Proteins/administration & dosage/immunology Neoplasm Transplantation Peptide Fragments/administration & dosage/chemical synthesis/*immunology T-Lymphocytes, Cytotoxic/*immunology Titrimetry Tumor Cells, Cultured/transplantation
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