Characterization of mouse MAGE-derived H-2Kb-restricted CTL epitopes.
Immunogenic peptide epitopes from tumor-associated antigens serve as targets for cellular immune responses in numerous clinical trials for therapeutic vaccinations. From these it became evident that prevailing questions can only be addressed in animal models. Hence, problems arise from the fact that while for human melanoma many different immunogenic peptide epitopes are known, for mouse melanoma the available selection is very restricted. To overcome this limitation, we applied reverse immunology to identify Kb-restricted epitopes derived of mouse MAGE. Two epitopes which bind strongly to Kb were selected to test for their immunogenicity in vivo. Spleen cells from mice vaccinated by intradermal injection of mature dendritic cells pulsed with these peptides displayed reactivity to the respective epitopes as measured by enzyme-linked immunospot assays and tetramer staining. The processing and presentation of these epitopes was evident by the killing of melanoma cells by the vaccination-induced T cells. Moreover, intravenous challenge with syngeneic melanoma cells demonstrated the protective immunity induced by this vaccination. In summary, we demonstrate the immunogenicity of two Kb-restricted peptide epitopes derived from mouse MAGE proteins which may serve as valuable tool for preclinical evaluation of vaccination strategies.
Eggert
Andreas O
AO
Department of Dermatology, Julius Maximilians-University Würzburg, Würzburg, Germany. eggert_a@klinik.uni-wuerzburg.de
Andersen
Mads H
MH
Voigt
Heike
H
Schrama
David
D
Kämpgen
Eckhardt
E
Straten
Per Thor
PT
Becker
Jürgen C
JC
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D045744:Cell Line, Tumor; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D007114:Immunization; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology; D058950:Melanoma-Specific Antigens; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009363:Neoplasm Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D007371:Interferon-gamma