title: Injection of irradiated b16 melanoma genetically-modified to secrete IFN-alpha causes regression of an established tumor.
abstract: Highly aggressive murine B16 melanoma was engineered to secrete IFN-alpha constitutively. Cells expressing IFN-alpha were injected into syngeneic C57BL/6 mice and the mice were monitored for tumor development. Secretion of IFN-alpha by B16 melanoma cells completely abrogated their tumorigenicity in syngeneic mice. LFN-alpha-secreting cells also abrogated the tumorigenicity of IFN-gamma-secreting and TNF-alpha-secreting cells when injected in combination whereas cells secreting either IFN-gamma or TNF-alpha grow progressively in mice when injected alone. Moreover, protected animals developed significant immunity against subsequent challenge with parental cells. Injection of parental cells and IFN-alpha-secreting cells together in a mixed tumor transplantation assay resulted in a significant reduction of tumorigenicity of the parental cells. Histopathological studies of the tissues from the injection site of the mice inoculated with a combination of parental and B16.IFN-alpha cells revealed the existence of a massive cellular infiltrate composed of lymphocytes and granulocytes at an early stage (7-11 days). In the later stages (22 days), no recognizable tumor tissue was detected. Injection of irradiated IFN-alpha-secreting cells in the mice carrying an established tumor completely prevented tumor development in 80% of the treated mice when injection was performed on the same side as the tumors. Injection of irradiated IFN-alpha-secreting cells in the contralateral site showed much less effect on the established tumor. Systemic antitumor effects on the established tumor can be enhanced by using a combination of irradiated IFN-alpha and IFN-gamma secreting cells as a vaccinating inoculum.
authors.affiliation: UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT MOLEC GENET & MICROBIOL,PISCATAWAY,NJ 08854. COLUMBIA UNIV,COLL PHYS & SURG,NEW YORK,NY.
authors.forename: S
authors.initials: S
authors.lastname: Sarkar
authors.forename: I
authors.initials: I
authors.lastname: Flores
authors.forename: Y
authors.initials: Y
authors.lastname: Ron
authors.forename: C
authors.initials: C
authors.lastname: Derosa
authors.forename: L
authors.initials: L
authors.lastname: Ozzello
authors.forename: S
authors.initials: S
authors.lastname: Pestka