Cancer vaccine design: a novel bacterial adjuvant for peptide-specific CTL induction.

Abstract	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-A0201/K(b) transgenic mice immunized with peptides derived from two melanoma-associated differentiation Ags, the HLA-A0201-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.
Authors	I Miconnet, I Coste, F Beermann, J F Haeuw, J C Cerottini, J Y Bonnefoy, P Romero, T Renno
Journal	Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 166 Issue 7 Pg. 4612-9 (Apr 01 2001) ISSN: 0022-1767 [Print] United States
PMID	11254719 (Publication Type: Journal Article)
Chemical References	Adjuvants, Immunologic Antigens, Neoplasm Bacterial Outer Membrane Proteins Cancer Vaccines Drug Combinations Epitopes, T-Lymphocyte MART-1 Antigen Macromolecular Substances Mlana protein, mouse Neoplasm Proteins Peptide Fragments Intramolecular Oxidoreductases dopachrome isomerase
Topics	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 MART-1 Antigen 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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