Transfection of cytokine genes to enhance tumor specific immunity: IL-3 enhancement of CTL activity is mediated by CD4 positive cells (Meeting abstract).

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Transfection of cytokine genes to enhance tumor specific immunity: IL-3 enhancement of CTL activity is mediated by CD4 positive cells (Meeting abstract).

Human Gene Ther; 3(5):609 1992. Unique Identifier : AIDSLINE ICDB/94698479
Pulaski B; McAdam A; Hutter E; Biggar S; Lord EM; Frelinger JG; Dept. of Microbiology and Immunology, Univ. of Rochester Sch. of; Medicine and Dentistry, 601 Elmwood Ave., Rochester, NY, 14642

Abstract: We have investigated the effects of expression of mouse IL-3, a cytokine involved in the maturation of T cells, upon the generation of immune effectors capable of killing untransfected tumors. Unlike systemic treatments, potent immunological mediators such as IL-3 and IL-2 can be delivered at the local site where the immune response is occurring via transfection of tumor cells. With this transfection strategy, we have begun to determine the effects of the cytokines on the type and the number of effectors generated within the tumor milieu. Using the line 1 lungs carcinoma as a model system and IL-3 and IL-2 driven by the beta-actin promoter, we have created line 1 transfectants which express high levels of IL-3 (2000 units/ml) or IL-2 (200 units/ml). These levels of IL-3 or IL-2 expression significantly enhance the ability of syngeneic mice to reject the transfected tumors. Tumor infiltrating lymphocytes (TILs) purified using paramagnetic beads from line 1 tumors transfected with either IL-3 or IL-2 expression vectors show a dramatically enhanced CTL response to untransfected parental line 1 when compared to TILs isolated from parental tumors. IL2, but not IL-3, expression by the tumors enhances the killing YAC-1 cells. To investigate the cells required for the generation of cytotoxic effectors, mice were depleted of CD4 or CD8 cells by in vivo treatment with anti-CD4 or anti-CD8 monoclonal antibodies. CD8 depletion abrogated the generation of cytotoxic effectors in all cases. Interestingly, CD4 depletion abrogated the IL-3 mediated CTL response but not the IL-2 mediated response. These results strongly suggest that IL-3, unlike IL-2, works to generate CTL by a mechanism which requires CD4 cells. Possible mechanisms for this effect will be discussed.

Keywords: Animal *Cytotoxicity, Immunologic/DRUG EFFECTS CD4-CD8 Ratio *Immunotherapy Interleukin-2/METABOLISM Interleukin-3/*GENETICS/METABOLISM/PHARMACOLOGY Lung Neoplasms/*IMMUNOLOGY/THERAPY Lymphocyte Depletion Lymphocytes, Tumor-Infiltrating/IMMUNOLOGY T-Lymphocytes, Cytotoxic/DRUG EFFECTS/*IMMUNOLOGY *Transfection Tumor Cells, Cultured ABSTRACT
940430
M9440915

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