UP-REGULATION OF TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION BY RETROVIRALLY TRANSDUCED HUMAN TUMOR-INFILTRATING LYMPHOCYTES USING TRANS-RETINOIC ACID

The ability of retinoic acid (RA) to upregulate gene expression in hum an tumor-infiltrating lymphocytes (TIL) transduced with a Moloney muri ne leukemia virus containing the cDNA encoding tumor necrosis factor ( TNF) has been studied. TNF production was increased approximately twof old after treatment with RA. This increase was dose dependent and corr esponded to a rise in the level of LTR-driven mRNA measured by Norther n analysis. RA did not appreciably increase transcription by the SV40 promoter or increase endogenous TNF production. The effect lasted for 3-6 days following withdrawal of RA. These studies indicate that RA ca n upregulate LTR-driven gene expression in TIL cells bearing retrovira l vectors and may thus be of use in studies of the gene therapy of can cer. (C) 1994 Academic Press, Inc.