combination therapy with fumagillin and vaccination with tumor-derived antigenic peptides in B16 melanoma-transplanted mice.
We established the antigen-presenting cell line RMA-S/mCD80 expressing mouse CD80. RMA-S is an antigen processing-defective mutant originating from RMA lymphoma and can be loaded with exogenous immunogenic peptides on the major histocompatibility complex class I (MHC-I) molecules. After immunization with RMA-S or RMA-S/mCD80 loaded with B16 melanoma-derived peptides, only RMA-S/mCD80 pulsed with B16 melanoma-derived peptides showed antitumor effects against B16 melanoma in vivo. However, it showed little enhancement of survival. On the other hand, fumagillin, an inhibitor of angiogenesis, suppressed B16 melanoma growth and showed a survival promoting effect. Combination therapy with fumagillin and vaccination with B16 melanoma-derived peptides strongly inhibited tumor growth and promoted survival more than fumagillin therapy alone. These results suggest that vaccination with poorly immunogenic tumor-derived peptides combined with antitumor drugs, such as anti-angiogenic compounds, may be useful.
Discovery Research Division, Santen Pharmaceutical Co., Ltd., Osaka, Japan.
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Tsuji
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Yamada
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000938:Antigen-Presenting Cells / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology*; D019496:Cancer Vaccines / Q000494:pharmacology*; D003131:Combined Modality Therapy; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D008546:Melanoma, Experimental / Q000098:blood supply / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D012717:Sesquiterpenes
D000900:Anti-Bacterial Agents; D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D019496:Cancer Vaccines; D003510:Cyclohexanes; D005231:Fatty Acids, Unsaturated; D012717:Sesquiterpenes; C026211:fumagillin