src-specific immune regression of Rous sarcoma virus-induced tumors.
We have developed an oncogene-specific tumor regression system in chickens. Injection s.c. of chicken wing webs with either rASV1702 or rASV157, mutants of Rous sarcoma virus (RSV) that express nonmyristolyated src product containing novel N-terminal domains, results in noninvasive fibrosarcomas that regress fully. The ability of challenge infections with wild-type RSV to form tumors is suppressed. This protective effect was shown to be specific for determinants encoded or induced by v-src (I. Gelman and H. Hanafusa, J. Virol., 61: 2461-2468, 1989). In the current study, we used SC chickens, inbred for major histocompatibility complex Class I haplotype B2/B2, to investigate whether this protection results from active immunity. Preinoculation of chickens with either replication-defective rASV1702 virus or non-virus-producing syngeneic chicken embryo fibroblasts expressing 1702src conferred protection against challenge infections with RSV. Thus, viremia was not required for this protection. Splenic lymphocytes from rASV1702-infected donors could transfer protective immunity against RSV tumor challenge to naive chickens. These lymphocytes were cytotoxic in vitro against RSV- or rASV1702-infected SC-chicken embryo fibroblasts, but not against SC-chicken embryo fibroblasts infected with helper virus, suggesting a specificity for src-encoded or -induced determinants. In contrast, splenic lymphocytes from RSV-infected chickens transferred protective immunity poorly and exhibited low in vitro cytotoxic potential for src determinants, suggesting possible suppression mechanisms. Finally, murine cell lines expressing 157src or 1702src produced tumors in nude mice that failed to regress. Thus, although cells expressing 157src or 1702src are inherently tumorigenic, the tumors they induce most likely regress due to immune mechanisms. These results suggest that 1702src and 157src induce src-specific tumor Ag that potently prime an oncogene-specific protective cellular immunity.
Gelman
I H
IH
Department of Microbiology, Mount Sinai Medical Center, New York, New York 10029.
Hanafusa
H
H
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D001358:Avian Sarcoma Viruses / Q000145:classification / Q000235:genetics; D002472:Cell Transformation, Viral / Q000276:immunology*; D002645:Chickens; D016391:Genes, src / Q000276:immunology*; D007111:Immunity, Cellular; D016219:Immunotherapy, Adoptive; D008214:Lymphocytes / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D001357:Sarcoma, Avian / Q000276:immunology* / Q000628:therapy
D000951:Antigens, Neoplasm