Establishment of a human fibroblast cell line producing tumor necrosis factor α (KMST-6/TNF) and growth inhibitory effects of its conditioned medium on malignant cells in culture

Abstract

To develop a new gene therapy model for cancer, a clonal cell line (KMST-6/TNF) which produces human tumor necrosis factor alpha (hTNF-alpha) has been developed by introducing hTNF-alpha cDNA into a human immortal fibroblast cell line (KMST-6). The conditioned medium (CM) of KMST-6/TNF cells inhibited the growth of various malignant human cell lines, but not that of normal human fibroblasts. Although the growth inhibitory effects of KMST-6/TNF CM were neutralized to a considerable degree by anti-TNF-alpha antibody, its inhibitory effects were more marked than the purified human natural TNF-alpha itself in the same units, suggesting that KMST-6/TNF CM contains some growth inhibitory substances other than TNF-alpha. However, interferons alpha, beta, and gamma were undetectable in the KMST-6/TNF CM.

Tumor necrosis factor as an antineoplastic agent: pitfalls and promises

“…These and other findings indicate the potential for using TNF gene-transduced tumor cells as a vaccine [113]. Others transfected fibroblasts with the TNF gene and showed that these cells started to produce TNF and had antitumor activities [114]. Intratumoral injection of the TNF gene in a suitable vector and concomitant irradiation resulted in a complete tumor regression in over 70% of xenografted malignant human gliomas in athymic nude mice [115].…”