Antitumor activity of murine tumor necrosis factor (TNF) against transplanted murine tumors and heterotransplanted human tumors in nude mice

Abstract

The antitumor activity of highly purified tumor necrosis factor (TNF) was tested against eight kinds of murine tumor and five kinds of human tumor heterotransplanted into nude mice. Mice were treated by intravenous or intratumoral injection of TNF, commencing when the tumors were well established. TNF showed an excellent curative effect against all kinds of murine and human tumors tested. Meth A sarcoma, Colon 26, Ehrlich, sarcoma 180, MM 46, MH 134, B16 melanoma, and Lewis lung tumors transplanted into mice underwent tumor necrosis and regression following a single injection of TNF. Sometimes a complete cure was observed in Meth A sarcoma, sarcoma 180, Ehrlich, and MM 46 tumors. Human cancers, SEKI, HMV-I, KATO-III, MKN 45, or KB, heterotransplanted into nude mice, also exhibited tumor necrosis and regression in size following several intratumoral injections of TNF. A great difference in curative effects of TNF was observed in Meth A sarcomas between those transplanted into BALB/c nu/+ and into BALB/c nu/nu mice: following a single intravenous administration the effect was stronger in BALB/c nu/+ than in nu/nu mice. In contrast, tumor necrosis was almost the same in nu/+ and nu/nu mice following intratumoral administration. The present results thus indicate that TNF from mice had an antitumor activity against not only murine tumors but also human tumors. In addition to direct cytotoxicity against tumor cells, TNF induced a host-mediated factor which contributed to the antitumor effects.

Interleukin 1 and tumour necrosis factor alpha may be responsible for the lytic mechanism during anti-tumour antibody-dependent cell-mediated cytotoxicity

“…Activated monocytes are known to secrete cytokines such as tumour necrosis factor alpha (TNF-a) (Carswell et al. 1975: Haranaka et al. 1984: Feinman et al.…”

Evaluation of recombinant human tumor necrosis factor by scheduled intratumoral administration in mice bearing transplantable tumors.

“…This observation supports previous findings that both gene-cloned and natural TNF elicits significant necrotic responses of Meth A-bearing BALB/c mice with single administration intralesionally or i.v. (Carswell et al 1975;Haranaka et al 1984;Pennica et al 1984). Hayashi et al (1986) reported that when rTNF was administrated i.v., rTNF markedly accumulates the tumor tissue and the half life Carswell et al (1975) reported that the maximal necrotic response induced by serum containing TNF was observed on day 7 at which the transplants were established well, and less effective on day 5 or 6.…”

A novel human tumor necrosis factor alfa mutein, F4614, inhibits in vitro and in vivo growth of murine and human hepatoma: Implication for immunotherapy of human hepatocellular carcinoma

“…Anti-tumor activity against solid tumors was expressed as mean tumor weights. Tumor weight, as derived from caliper measurements of the length (L) and width (W) of the tumors, and the length (l) and width (w) of tumor necrosis in mm, was calculated as follows 26 :…”