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KMID : 0578319950050060595
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Molecules and Cells
1995 Volume.5 No. 6 p.595 ~ p.604
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Murine Sarcoma Cells Transfected with Unterleukin 12 are Rejected in vivo Inducing Protective and Curative Immune Responses against the Parental Cells
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Park, joo-Hung
Chang, Sun-Hee/Lee, kwang-Min/Lee, Hern-Ku
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Abstract
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We evaluated the in vivo antitumor activity of interleukin 12 (IL-12) in a murine sarcoma model using gene transfer techniques. M-MSV-BALB/3T3 clone engineered to secrete IL-12 was rejected when transplanted into syngeneic BALB/c mice. The tumors rejected in vivo not only induced protective immunity against subcutaneous growth or pulmonary metastases of the parental, nontransfected tumor cells, but also induced curative immunity against established subcutaneous tumors. A generation of CTL activity was significantly induced by injection of IL-12-secreting tumor cells. The wild-type and IL-12-secreting tumor cells grew equally well in nude mice, implying that T-lymphocytes could play a major role in mediating the antitumor effects of IL-12. Adoptive transfer experiments subsequently identified both CD4^(+) and CD8^(+) T-cells an the major mediators. It was also shown that tumor cells transiently expressing IL-12 were as potent as stable transformants in causing the antitumor activity of IL-12. The results described in the present studies indicate that IL-12 secreted from tumor cells is a potent mediator in induction of protective as well as curative immune responses against the parental cells in vivo.
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KEYWORD
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