TRANSDUCTION OF HUMAN RENAL-CARCINOMA CELLS WITH HUMAN GAMMA-INTERFERON GENE VIA RETROVIRAL VECTOR

We used a retroviral vector containing a human gamma-interferon (gamma -IFN) gene to transduce 13 renal carcinoma cell lines. The transductio n efficiencies ranged from 0% to 60%, as determined by using an analog ous vector containing the LacZ marker gene. In addition, gene-transfer red resistance to the antibiotic neomycin was used to select for trans duced cells. Nine of 13 lines were successfully transduced. Transducti on was associated with the morphologic change of elongation, and there was a marked decrease in cell growth rate. Transduced cells secreted varying amounts (20-1076 pg/10(6) cells/d) of gamma-IFN as measured by enzyme-linked immunosorbent assay for at least 2 to 3 weeks after tra nsduction (including 1 day of transduction, 6-7 days of selection, and an additional 8-12 days before the first passage of the transduced ce lls). Human leukocyte antigen (HLA) class II expression was markedly i ncreased in six of seven cell lines; HLA class I expression was signif icantly increased in two of eight lines. Transduced cells that were su bjected to cryopreservation after irradiation still produced gamma-IFN and expressed HLA class I and II antigens, although generally al lowe r levels than before these manipulations. This study confirms that ret roviral vector transduction of the human gamma-IFN gene into renal car cinoma cells is feasible and associated with persistent production of gamma-IFN and increased expression of HLA class I and II molecules, an d these effects are retained after irradiation and cryopreservation. T his suggests that an autologous tumor cell vaccine trial with irradiat ed gamma-IFN gene-transduced renal carcinoma cell is rationale and fea sible.