Antiproliferative effects of natural interferon beta alone and in combination with natural interferon gamma on human breast carcinomas in nude mice

Abstract

Nude mice bearing bilateral xenografts of human breast carcinoma cells (MCF-7 and BT20) were treated with 2 or 45-day cycles of intralesional (i.l.) injections of human natural interferon beta (nIFN-beta) alone or in combination with human natural interferon gamma (nIFN-gamma). The injections were administered to only 1 of the 2 tumors in each animal, thus making it possible to assess at the same time local therapeutic effects in the injected tumors and systemic effects in the contralateral ones. When n-IFN-beta was used as a single agent only mild local antitumor effects and virtually no systemic effects were observed. In contrast, the combined administration of nIFN-beta/nIFN-gamma produced marked antiproliferative effects, presumably as a result of the synergistic action of type I and type II IFNs. These effects ranged from complete regression documented histologically in 2 MCF-7 tumors to varying degrees of growth inhibition with persistence of residual microscopic or grossly detectable tumor. Local effects were more pronounced than systemic effects. The therapeutic efficacy of nIFN-beta proved to be greater than that of recombinant interferon beta (rIFN-beta). In MCF-7 tumors nIFN-beta appeared to be less effective than nIFN-alpha, whereas the opposite was true for BT20 tumors.

A functional in vitro model of heterotypic interactions reveals a role for interferon-positive carcinoma associated fibroblasts in breast cancer

“…The role of interferons in modulating the immune response to viruses is well known, but the role of interferons in modulating the immune response to tumors is less well defined. Early experimental models have uncovered potent direct cytotoxic and/or anti-proliferative effects of interferons [ 24 - 27 ], although the translation of these findings into their use as anti-cancer therapeutics [ 28 - 30 ] has been met with only limited success in breast cancer [ 30 ] and other carcinomas [ 31 ]. In fact, there were even early indications that the administration of IFN-β to cancer patients could lead to an increase in the number of hormone receptors in the cancerous tissue [ 32 ].…”

Mullerian Inhibiting Substance Promotes Interferon γ-induced Gene Expression and Apoptosis in Breast Cancer Cells

“…IFN-␥ in combination with IFN-␤ has been shown to induce the regression of human breast cancer cell lines MCF7 and BT20 grown as xenografts in nude mice (58). Although the antitumor effect of IFN-␥ in vivo has been well documented, toxicity associated with exposure to IFN-␥ has diminished its utility in treatment (59).…”

Specific immunotherapy against occult cancer metastases

“…Extensive clinical trials led to the conclusion that IFNs can be efficacious against some hematopoietic and vascular neoplasms 45, 46, 47. Systemic IFN therapy for most solid tumors, however, has produced only limited responses,48, 49, 50, 51 probably because of insufficient accumulation of biologically active IFN in tumors 49, 52, 53. This hypothesis is supported by a pharmacokinetics study showing that the half‐life of IFN‐β in the circulation of humans is about 5 min.…”