Development and characterization of an interleukin-2-transduced human ovarian carcinoma tumor vaccine not expressing major histocompatibility complex molecules.

Abstract

We initiated studies to develop cytokine-secreting human ovarian carcinoma cells for the purpose of using these cells as vaccines for the treatment of advanced epithelial ovarian cancer. A human ovarian carcinoma cell line (UCI-107) was genetically engineered to secrete the cytokine interleukin-2 by retroviral-mediated gene transduction. One clone, termed UCI-107A IL-2 AS, constitutively secreted high levels of interleukin-2 (i.e., 2000 to 2300 pg/ml/10(5) cells per 48 hours) for > 55 passages and 8 months of study. Unlike parental- and vector-transduced cells, UCI-107A IL-2 AS cells were aneuploid and failed to express major histocompatibility complex class I and HER2/neu surface antigens. UCI-107A IL-2 AS cells were highly resistant to killing by gamma irradiation and continued to produce high levels of interleukin-2 even after irradiation with 10,000 cGy. Balb/C nude mice injected intraperitoneally with UCI 107-A IL-2 AS cells survived significantly longer than control animals, with 25% of the animals totally rejecting their tumors. UCI-107A IL-2 AS was totally resistant to killing by fresh allogeneic peripheral blood lymphocytes in four hour chromium 51 release assays but induced high levels of killing in 72-hour long-term cytotoxic assays. The potential use of these interleukin-2-secreting ovarian carcinoma cells as vaccines for women with advance ovarian cancer will be discussed.