title: Irradiated NC adenocarcinoma cells transduced with both B7.1 and interleukin-2 induce CD4+-mediated rejection of established tumors.
abstract: Previous studies have shown that expression of the immune co-stimulator B7.1 reduces the tumorigenicity of some, but not all, malignant cell lines. However, B7.1-expressing tumor cells are not very effective in inducing the rejection of established tumors. This may in part be due to induction of anergy in the potentially reactive T cells. Previous studies have shown that IL-2 can reverse the anergic state both in vitro and in vivo. Therefore, we have examined the effect of retrovirus-mediated delivery and expression of murine B7.1 and interleukin-2 on tumor formation and rejection of established MHC class I+/II- NC adenocarcinomas. Neither the expression of B7.1 nor IL-2 alone had a significant effect on NC tumorigenicity. In contrast, combined expression of B7.1 and IL-2 substantially decreased the tumorigenicity of these cells in the immunecompetent syngeneic hosts. T-cell depletion studies show this to be dependent primarily on the activation of CD4+ cells. Furthermore, distant subcutaneous injection of irradiated NC/IL-2/B7.1 can induce, much more effectively than NC/B7.1 or NC/IL-2, the rejection of small NC tumors, and prevent the recurrence of large surgically resected tumors. Together, these results suggest that tumor cells genetically modified to express B7.1 and IL-2 can induce the immune-mediated rejection of established class II- tumors by a mechanism involving CD4+ cells.
authors.affiliation: Department of Molecular Medicine, King's College School of Medicine & Dentistry, London, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Gaken
authors.forename: S J
authors.initials: SJ
authors.lastname: Hollingsworth
authors.forename: W J
authors.initials: WJ
authors.lastname: Hirst
authors.forename: A G
authors.initials: AG
authors.lastname: Buggins
authors.forename: J
authors.initials: J
authors.lastname: Galea-Lauri
authors.forename: M
authors.initials: M
authors.lastname: Peakman
authors.forename: M
authors.initials: M
authors.lastname: Kuiper
authors.forename: P
authors.initials: P
authors.lastname: Patel
authors.forename: P
authors.initials: P
authors.lastname: Towner
authors.forename: P M
authors.initials: PM
authors.lastname: Patel
authors.forename: M K
authors.initials: MK
authors.lastname: Collins
authors.forename: G J
authors.initials: GJ
authors.lastname: Mufti
authors.forename: F
authors.initials: F
authors.lastname: Farzaneh
authors.forename: D C
authors.initials: DC
authors.lastname: Darling
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D018122:B7-1 Antigen / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007223:Infant; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000628:therapy; D051379:Mice; D008815:Mice, Inbred Strains; D016513:Mice, SCID; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D007376:Interleukin-2