title: Induction of cytotoxic T lymphocytes specific for a syngeneic tumor expressing the E6 oncoprotein of human papillomavirus type 16.
abstract: Human papillomavirus (HPV) type 16 has been implicated in the etiology of cervical carcinomas, but it is unknown whether HPV-specific immunity can function in controlling the growth of HPV-associated carcinomas. We previously demonstrated that CD8+ T lymphocytes can inhibit the in vivo outgrowth of murine tumor cells transfected with the HPV-16 E7 gene and have now established a murine model to study the CTL responses to the E6 oncoprotein of HPV-16. Immunization of C3H/HeN mice with syngeneic fibroblasts expressing a transfected HPV-16 E6 gene induced regression of transplanted tumors expressing this gene. Populations of CTL isolated from the spleens of mice whose E6+ tumors had regressed were shown to specifically lyse E6+ target cells. The cytolytic activity was mediated by CD8+ CTL in a MHC restricted pattern. These data and our previous findings with transfected tumor cells expressing the E7 gene, support the conclusion that tumor cells associated with HPV-16 can be inhibited by CTL specific for molecules encoded by the HPV-16 E6 and E7 genes.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.forename: M T
authors.initials: MT
authors.lastname: Mizuno
authors.forename: M C
authors.initials: MC
authors.lastname: Singhal
authors.forename: S L
authors.initials: SL
authors.lastname: Hu
authors.forename: D A
authors.initials: DA
authors.lastname: Galloway
authors.forename: I
authors.initials: I
authors.lastname: Hellström
authors.forename: K E
authors.initials: KE
authors.lastname: Hellström
mesh_terms: D000818:Animals; D001483:Base Sequence; D016827:CD8 Antigens / Q000032:analysis; D002460:Cell Line; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000382:microbiology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D016827:CD8 Antigens; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16