Cancer vaccine design: a novel bacterial adjuvant for peptide-specific CTL induction.
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.
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Switzerland.
I
I
Miconnet
I
I
Coste
F
F
Beermann
J F
JF
Haeuw
J C
JC
Cerottini
J Y
JY
Bonnefoy
P
P
Romero
T
T
Renno
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000138:chemical synthesis; D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D004338:Drug Combinations; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D016233:Immunotherapy, Active / Q000379:methods; D007279:Injections, Subcutaneous; D019746:Intramolecular Oxidoreductases / Q000008:administration & dosage / Q000276:immunology; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008212:Lymphocyte Depletion; D058965:MART-1 Antigen; D046911:Macromolecular Substances; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000008:administration & dosage / Q000276:immunology; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D017186:Titrimetry; D014407:Tumor Cells, Cultured / Q000637:transplantation
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D001425:Bacterial Outer Membrane Proteins; D019496:Cancer Vaccines; D004338:Drug Combinations; D018984:Epitopes, T-Lymphocyte; D058965:MART-1 Antigen; D046911:Macromolecular Substances; C548668:Mlana protein, mouse; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase