DEVELOPMENT AND CHARACTERIZATION OF AN IL-4-SECRETING HUMAN OVARIAN-CARCINOMA CELL-LINE

Human ovarian carcinoma cell lines were genetically engineered to secr ete the cytokine interleukin-4 (IL-4) by retroviral-mediated gene tran sduction. These cells were transduced with the LXSN retroviral vector containing the human IL-4 gene and the neomycin resistance selection m arker. Numerous IL-4-secreting clones were isolated from different pap illary serous carcinoma cell lines, including SKOV-3, UCI-101, and UCI -107, and one clone derived from UCI-107 extensively characterized. Th is clone, termed UCI 107E IL-4 GS, was shown to constitutively express high levels of IL-4 (i.e., 900 to 1300 pg/ml/10(5) cells/48 hr) for o ver 35 passages and 6 months of study. Like the parental cell line (UC I-107), UCI 107E IL-4 GS cells expressed MHC class I and Her-2/neu sur face antigens but did not express detectable MHC class II, ICAM 1, CA 125, or IL-4 receptors. No increase in expression of surface proteins was noted between parental and UCI 107E IL-4 GS. The morphology of thi s done did not differ from that of the parental or LXSN vector control cells; however,parental cells had a faster growth rates than transduc tants, UCI 107E IL-4 GS was sensitive to gamma irradiation since as li ttle as 2500 rad killed most of the cells within 10 days of irradiatio n, However, after irradiation, IL-4 secretion continued until about Da y 8. The potential use of these IL-4-secreting ovarian carcinoma cells as vaccines for woman with advanced ovarian cancer will be discussed. (C) 1995 Academic Press, Inc.