New Advances in Interferon Therapy of Cancer

Abstract

Substantial increases in both the understanding of the cellular mechanisms of actions of interferon (IFN) and in its clinical use in cancer have occurred in recent years. The efficacy of interferon for the treatment of select malignancies has been established, and IFN‐α and IFN‐β have been approved by the Food and Drug Administration for multiple clinical indications. IFN‐α increased median survival and relapse‐free survival in patients with locally advanced melanoma when used as adjuvant therapy and had modest activity against advanced disease. In other tumors where studies indicated that IFN lacked direct therapeutic activity, clinical trials suggested that it increased the antitumor activity of cytotoxic chemotherapeutic agents when used in combination therapy. IFN has substantial activity in chronic myelogenous leukemia, increasing survival in patients in early chronic phase when compared with conventional chemotherapy, and has some activity in non‐Hodgkin's lymphoma in combination with cytotoxic agents. Recent molecular and pharmacologic studies defining cellular receptor activation, signal transduction pathways, and biochemical modulating activities of interferon have yet to be fully incorporated into clinical development. Further preclinical advances along with the expanding identification of potentially clinically sensitive tumors make it likely that the use of IFN in cancer chemotherapy will continue to grow.

Effect of recombinant feline interferon‐ω alone and in combination with chemotherapeutic agents on putative tumour‐initiating cells and daughter cells derived from canine and feline mammary tumours

“…IFNs act at different molecular and cellular levels of potential relevance in cancer by a direct and indirect (host‐mediated) activity. A direct antiproliferative effect is mediated by inhibition of cell cycle progression, modulation of the expression of oncogenes and tumour suppressor genes, downregulation of cell surface receptors for growth factors and inhibition of the early‐growth factor‐mediated events 10,23,24 …”

“…IFNs inhibit cell cycle progression and thereby can be considered antiproliferative agents 10 . Feline and canine daughter cells and TICs were sensitive to the direct antitumour effect of rFeIFN‐ω.…”

“…Immunotherapy with interferon (IFN)‐α and IFN‐β has been shown to prolong the survival of human patients with metastatic breast cancer and other selected malignancies 9,10 . The antitumour effect of IFN‐ω (IFN‐ω) has not been well described compared with other type I INFs (α and β) with a limited number of in vitro and in vivo studies.…”

The role of rational immunotherapy for renal cell carcinoma

“…The results of the randomized studies, which have been completed to date involving interferon alfa based regimens, clearly indicate that interferon alfa is active in this disease. Patients who are most likely to respond and who should be offered interferon alfa therapy are those who are less than 70 years old, with good performance status, and metastases in either the lungs or the lymph nodes (17,18). Various studies have attempted to identify other possible prognostic factors, which could be used to identify patients most likely to benefit from interferon alfa based therapy (4,6,17,18).…”

“…Patients who are most likely to respond and who should be offered interferon alfa therapy are those who are less than 70 years old, with good performance status, and metastases in either the lungs or the lymph nodes (17,18). Various studies have attempted to identify other possible prognostic factors, which could be used to identify patients most likely to benefit from interferon alfa based therapy (4,6,17,18). Future advances in interferon therapy are likely to be based on emerging information about the cellular actions of interferon and interferon-related signal transduction pathway.…”