Tumor cells expressing a recall antigen are powerful cancer vaccines.
Tumor cells were engineered to express a specific recall antigen molecule to serve as a target for the host's existing memory response, and then used as immunogens as a novel form of cancer vaccine. As recall antigen, the efficiently expressible hybrid protein Heat1 was employed, that contains an antigenic fragment of the Mycobacterium bovis 65-kDa heat shock protein (hsp65), and thus can be recognized in mice immunized with live Bacillus Calmette-Guérin (BCG) or its derivatives. Mouse M-3 melanoma cells were transfected to express Heat1, irradiated, and used as anti-melanoma vaccines. Vaccination elicited anti-tumor immunity in mice, i.e. a subsequent challenge with the parental wild-type M-3 melanoma cells was rejected. Successful vaccination was dependent on the correct recognition of the recall antigen, since vaccination failed to prevent outgrowth of the challenge in mice possessing no memory response against the recall antigen. The results indicate that expression of a recall antigen can turn tumor cells into powerful vaccines. By using the Heat1 protein or other appropriate antigens, this general concept may be applied for human therapy.
Schweighoffer
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Research Institute for Molecular Pathology, Vienna, Austria.
D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D001426:Bacterial Proteins; D019496:Cancer Vaccines / Q000276:immunology*; D018834:Chaperonin 60; D018833:Chaperonins / Q000096:biosynthesis / Q000276:immunology*; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008546:Melanoma, Experimental / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008811:Mice, Inbred DBA; D014407:Tumor Cells, Cultured
D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D019496:Cancer Vaccines; D018834:Chaperonin 60; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins