Treatment of breast cancer with fibroblasts transfected with DNA from breast cancer cells

This investigation was based on the hypothesis that weakly immunogenic, bre ast cancer-associated Ags, the products of mutant or dysregulated genes in the malignant cells, will be expressed in a highly immunogenic form by semi allogeneic IL-2-secreting fibroblasts transfected with DNA from breast canc er cells. (Classic studies indicate that transfection of genomic DNA can st ably alter both the genotype and the phenotype of the cells that take up th e exogenous DNA,) To investigate this question, we transfected LM mouse fib roblasts (H-2(k)) modified to secrete IL-2 with genomic DNA from a breast a denocarcinoma that arose spontaneously ina C3H/He mouse (H-2(k)). To increa se their nonspecific immunogenic properties, the fibroblasts were also modi fied before transfection to express allogeneic MHC determinants (H-2K(b)), Afterward, the IL-2-secreting semiallogeneic cells were cotransfected with DNA from the spontaneous breast neoplasm, along with a plasmid (pHyg) confe rring resistance to hygromycin, Pooled colonies of hygromycin-resistant cel ls were then tested in C3H/He mice for their immunotherapeutic properties a gainst the growth of the breast neoplasm, The results indicated that tumor- bearing mice immunized with the transfected cells survived significantly lo nger than mice in various control groups. Similar beneficial effects were s een in C57BL/6 mice injected with a syngeneic breast carcinoma cell line (E O771) and semiallogeneic, IL-2-secreting fibroblasts transfected with DNA f rom EO771 cells. The immunity was mediated by CD8(+) T cells since immunize d mice depleted of CD8(+) cells failed to resist tumor growth.