Rejection of a nonimmunogenic melanoma by vaccination with natural melanoma peptides on engineered antigen-presenting cells.
Naturally processed peptides, obtained by acid extraction of tumor cells, contain Ags able to activate specific CTL in vitro. We recently reported that the nonprofessional APC, RMA-S, expressing the B7.1 molecule (RMA-S/B7), pulsed with naturally processed peptides from the nonimmunogenic B16F1 melanoma (B16F1a.e.) primed syngenic CD8+ T cells against the tumor in vitro. Here, we show the rejection of B16F1 melanoma by C57BL/6 mice after immunization with RMA-S/B7 cells pulsed with B16F1a.e. This response is critically dependent on both CD4+ and CD8+ cells, but not on NK cells. However, only CD8+ T cells exert anti-B16F1 cytolitic activity in vitro. Moreover, RMA-S/B7 cells pulsed with B16F1a.e. can be used to prevent the growth of 24-h preestablished melanomas. These results may have important implications for the clinical use of natural peptide fractions of tumor cells as therapeutic cancer vaccines.
Bellone
M
M
Laboratory of Tumor Immunology, San Raffaele Scientific Institute, School of Medicine, University of Milan, Italy. bellonem@hsr.it
Iezzi
G
G
Martin-Fontecha
A
A
Rivolta
L
L
Manfredi
A A
AA
Protti
M P
MP
Freschi
M
M
Dellabona
P
P
Casorati
G
G
Rugarli
C
C
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000276:immunology*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D019496:Cancer Vaccines; D014614:Vaccines, Synthetic