ABLATION OF TRANSPLANTED HTLV-I TAX-TRANSFORMED TUMORS IN MICE BY ANTISENSE INHIBITION OF NF-KAPPA-B

Mice transgenic for the human T cell leukemia virus (HTLV-1) Tax gene develop fibroblastic tumors that express NF-kappaB-inducible early genes. In vitro inhibition of NF-kappaB expression by antisense oligodeoxynucleotides (ODNs) inhibited growth of these culture-adapted Tax-transformed fibroblasts as well as an HTLV-I-transformed human lymphocyte line. In contrast, antisense inhibition of Tax itself had no apparent effect on cell growth. Mice treated with antisense to NF-kappaB ODNs showed rapid regression of transplanted fibrosarcomas. This suggests that NF-kappaB expression may be necessary for the maintenance of the malignant phenotype and provides a therapeutic approach for HTLV-I-associated disease.