697. Intratumoral Injection of Cytokine-Secreting Syngeneic/Allogeneic Fibroblasts Transfected with Tumor DNA Prolongs the Survival of Mice with an Intracerebral Tumor

Abstract

Top of pageAbstract Prior studies have revealed the immunotherapeutic properties of a vaccine prepared by transfer of genomic DNA from breast cancer cells into a highly immunogenic cell line. The rationale for this type of vaccine is that genes specifying an array of weakly immunogenic, unique tumor antigens associated with the malignant cells will be expressed in a highly immunogenic form by the transfected cells. Here, the immunotherapeutic properties of a vaccine prepared by transfection of mouse fibroblasts with DNA from a breast carcinoma (SB-5b) that arose spontaneously in a C3H/He mouse (H-2Kb) were tested in mice with intracerebral breast cancer. To augment their non-specific immunogenic properties, before DNA-transfer, the fibroblasts (of C3H/He mouse origin) were modified to express allogeneic MHC class I H-2Kb-determinants and to secrete IL-2, IL-18 or GM-CSF. The results indicate that C3H/He mice injected intracerebrally with the breast cancer cells and syngeneic/allogeneic transfected fibroblasts modified to secrete IL-2 survived significantly longer (P<0.005) than mice in various control groups, including mice injected intracerebrally with the breast cancer cells alone. The immunotherapeutic properties of transfected fibroblasts modified to secrete IL-18 or GM-CSF were less efficacious. The results of two independent in vitro cytotoxicity assays indicate that systemic cellular anti-tumor immunity was generated in mice injected intracerebrally with the transfected cells and the immunity was mediated predominantly by CD8+ T cells. This data suggests that syngeneic/allogeneic fibroblasts genetically engineered to secrete certain cytokines and to express tumor antigens are effective in stimulating an anti-tumor immune response and prolonging survival in mice with an intracerebral tumor upon injection of these cells directly into the tumor.