title: Variant mouse lymphoma cells with modified response to interferon demonstrate enhanced immunogenicity.
abstract: We have previously developed an experimental model for the xenogenization of malignant lymphoma. From highly tumorigenic S49 mouse lymphoma cells that proliferate in suspension culture (designated T-25), we selected variant clones that grew as an adherent monolayer (designated T-25-Adh) and were non-tumorigenic in syngeneic mice. Furthermore, priming of syngeneic hosts with T-25-Adh cells protected them against subsequent challenges with the tumorigenic T-25 cells. Several lines of evidence have indicated that antigens of an endogenous mouse mammary tumor virus (MMTV) are involved in the immunogenicity of T-25-Adh cells. Since interferon (IFN) is known to affect retroviral assembly and maturation on the cell membrane, we have studied the effects of IFN on endogenous MMTV-related structures, as well as on the immunogenicity of T-25-Adh cells. We observed that mouse alpha and beta interferons affect the morphogenesis of intracellular MMTV-related precursors in the immunogenic T-25-Adh cells, but not in tumorigenic T-25 cells. From T-25-Adh cells we selected variants that were either high responders or low responders to the above-mentioned interferon effect. The high-response variants were significantly more protective against tumorigenic T-25 cells than the low-response variants. Involvement of MMTV-related antigens in the immune response of the host to T-25-Adh cells was further suggested by immunoelectron-microscopical analysis, demonstrating that antisera from mice, immunized with T-25-Adh cells, interacted specifically with cell-surface MMTV budding particles. These findings indicate a novel method for xenogenization of lymphoma cells by IFN. Since endogenous retroviruses are present in all tissues of the mouse, this approach might be applicable to a wide variety of tumors.
authors.affiliation: Department of Cell and Animal Biology, Hebrew University of Jersualem, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Mador
authors.forename: H
authors.initials: H
authors.lastname: Falk
authors.forename: M
authors.initials: M
authors.lastname: Bergel
authors.forename: A
authors.initials: A
authors.lastname: Panet
authors.forename: J
authors.initials: J
authors.lastname: Hochman
mesh_terms: D000818:Animals; D000940:Antigenic Variation; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D007372:Interferons / Q000494:pharmacology; D008223:Lymphoma / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008324:Mammary Tumor Virus, Mouse / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D014185:Transplantation, Isogeneic; D014613:Vaccines, Attenuated
chemical_list: D019496:Cancer Vaccines; D014613:Vaccines, Attenuated; D007372:Interferons