Progress toward therapeutic application of interferons, 1979–1983

Abstract

Interferons differ chemically and biologically from other modalities of cancer treatment. They are proteins that inhibit viral replication, influence subcellular processes, slow cellular proliferation, affect cell differentiation, and modulate immune responses. These regulatory effects on cell function undoubtedly underlie the effects of interferons in malignant disease. As a result of efforts by academia, industry, governments, and organizations such as the American Cancer Society, significant progress has been made over the past 5 years in elucidating structure, improving production, and defining clinical applications of interferons for both virus and malignant disease.

Interferon-? inhibits proliferation and progression through S phase of the cell cycle in five glioma cell lines

“…This is consistent with previous studies [31][32][33] suggesting that gliomas are more sensitive to IFN-~ than IFN-o~. Although many cells exhibit an anti-proliferative response to IFN-7 [6,7,10,35], some, including a rat glioma cell line [36], astrocytes [37], T cells [38] and keratinocytes [39] have been shown to proliferate when treated with IFN-7. The observed proliferative response of AO2V4 and some other cells to IFN-yis likely attributed to the fact that IFN-7 binds to a different cell surface receptor and can activate different signal transduction pathways that are not activated by IFN-a/~ [35,40].…”

“…Since that time, these anti-viral agents have been found to exert an anti-tumor effect on a wide variety of, not only virally-induced tumors, but also tumors of varied etiology [6,7]. Each of the three IFNs, IFN-c~, IFN-[3 and IFN-y can have anti-tumor activity, however, cancers often respond differently to each type.…”

“…IFN-o~is currently the most widely used and is effective for treatment of many hematological malignancies as well as some solid tumors including Kaposi's sarcoma, renal-cell carcinoma and melanoma [8]. Two major mechanisms have been proposed to account for the anti-tumor activity of IFNs: 1) inhibition of cell proliferation and 2) modulation of the immune response [6][7][8][9][10][11]. Both mechanisms involve induction of proteins that mediate the anti-viral, anti-proliferative and immunoregulatory actions.…”

Pulmonary Sarcoidosis Following Interferon Therapy for Advanced Renal Cell Carcinoma

“…We believe that in this patient therapy with IFN may have played an important role in the pathogenesis of sarcoid because of the strong immune influences known to be induced by IFN and the well-known in vivo and in vitro immune changes seen in patients with sarcoidosis. l 3 We believe this to be the first reported association of metastatic RCC and pulmonary sarcoidosis in the same patient with IFNP possibly having a role in its pathogenesis.…”

Radiosensitizing effect of natural and recombinant β-interferons in a human lung carcinoma in vitro

“…It is supposed to be the result of a modulation of the immune response, a direct cytotoxic or cytostatic action on tumor cells, and an induction of dierentiation as shown for leukemia cells and squamous cell carcinoma cells (Borden 1984;Nair et al 1994;Lokshin et al 1995). However, the activity of IFNs as single substances has been disappointingly low in solid tumors (Wheeler et al 1994).…”