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.

journal_name

Int J Oncol

authors

Sarkar S,Flores I,Ron Y,Derosa C,Ozzello L,Pestka S

doi

10.3892/ijo.7.1.17

subject

Has Abstract

pub_date

1995-07-01 00:00:00

pages

17-24

issue

1

eissn

1019-6439

issn

1791-2423

journal_volume

7

pub_type

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