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The Journal of Immunology, 2001, 166: 4612-4619.
Copyright © 2001 by The American Association of Immunologists

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

Isabelle Miconnet*, Isabelle Coste{ddagger}, Friedrich Beermann{dagger}, Jean-François Haeuw{ddagger}, Jean-Charles Cerottini*, Jean-Yves Bonnefoy{ddagger}, Pedro Romero* and Toufic Renno1,{ddagger}

* Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, and {dagger} Swiss Institute for Cancer Research, Epalinges, Switzerland; and {ddagger} Centre d’Immunologie Pierre Fabre, Saint Julien-en-Genevois, France

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 Klebsellia pneumoniae (P40) for specific CTL induction. We studied the CTL response induced in HLA-A*0201/Kb transgenic mice immunized with peptides derived from two melanoma-associated differentiation Ags, the HLA-A*0201-restricted decapeptide Melan-A26–35 substituted at position 2 and the Kb-restricted tyrosinase-related protein 2181–188 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 2181–188 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.




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