title: Generation of an effective anti-tumor immunity after immunization with xenogeneic antigens.
abstract: Central and peripheral tolerance mechanisms are expected to hamper the generation of effective immunity against tumors. To break self tolerance against malignant gliomas, we assessed the therapeutic potential of self/foreign antigen cross-reactivity in an immunocompetent rat glioma model. Immunotherapy of tumors using xenogeneic human glioma membrane proteins (HGP) as a vaccine inhibited tumor growth, whereas no significant effect was obtained with rat glioma membrane proteins (RGP). In contrast to RGP, HGP elicited a specific IgG immune response that cross-reacted with RGP. This immune response was found to be mainly a Th1 type response. On tumor sections stained with hematoxylin and eosin, glioma cells are sparse and apoptotic in HGP-immunized rats, whereas control tumors showed condensed and viable cells. Tumor-specific CTL were induced in HGP-immunized rats. Immunohistochemical analysis revealed that a significant number of CD8(+) and CD4(+) cells infiltrated into tumors from HGP-vaccinated rats, whereas RGP vaccination led to only few tumor-infiltrating T cells. Taken together, the data establish the in vivo applicability of the cross-stimulation between self and foreign antigens as an alternative way to break tolerance against the poorly immunogenic gliomas.
authors.affiliation: Department of Immunology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway. mosioud@ulrik.uio.no
authors.forename: Mouldy
authors.initials: M
authors.lastname: Sioud
authors.forename: Dag
authors.initials: D
authors.lastname: Sørensen
mesh_terms: D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology; D002455:Cell Division; D005910:Glioma / Q000276:immunology* / Q000473:pathology; D006801:Humans; D009368:Neoplasm Transplantation; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014611:Vaccination
chemical_list: D015478:Antigens, Heterophile; D019496:Cancer Vaccines