Interferons: Anti-neoplastic drugs?

Strander, Hans

doi:10.1007/bf00996140

Cited by 135 publications

(31 citation statements)

References 89 publications

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“…The antitumor activity of interferons (32,33) is of clinical interest and may be in part due to an inhibitory effect on cell growth. We compared the effects of human type I and type II interferon preparations on a number of normal and transformed human cells (i) by measuring the incorporation of [3H]thymidine into DNA and (ii) by following their growth.…”

Section: Methodsmentioning

confidence: 99%

Differential efficacies of human type I and type II interferons as antiviral and antiproliferative agents.

Rubin¹,

Gupta²

1980

Proc. Natl. Acad. Sci. U.S.A.

244

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Treatment of human fibroblast FS4 cultures with human type II interferon preparations induced the synthesis of at least four proteins that were similar in size to four of the five proteins induced by type I interferons (Mr 120,000, 88,000, 67,000, and 56,000). However, the M, 67,000 and 56,000 proteins were induced more strongly by type II than by type I interferon, and a counterpart of a Mr 80,000 protein induced by type I interferons was not noticeably induced by type II interferon preparations. We therefore compared type I and type II interferons for relative antiviral activities against different viruses (vesicular stomatitis, encephalomyocarditis, and vaccinia viruses and reovirus) and for cell growth-inhibitory activities on various cell types. The replication of vesicular stomatitis and encephalomyocarditis viruses was inhibited more strongly by type I interferon, whereas reovirus and vaccinia virus showed greater sensitivity to type II interferon preparations. This indicates that viruses may differ in their sensitivity to human type I and type II interferons and that the antiviral mechanisms induced by type I and type II interferons may have significant differences. The type I and type II interferons may also differ in their efficacies as antiproliferative agents. Type II interferon preparations at 2.5 units/ml inhibited the incorporation of [3H]thymidine to a greater extent than did type I interferon at 400 units/ml. (For both type I and type II interferons, the unit of interferon activity was defined as the concentration that decreased the yield of vesicular stomatitis virus by 50% in FS-4 cultures.) Furthermore, whereas type II interferon preparations had a reversible cytostatic effect on normal human fibroblasts at 10 units/ml, the transformed cells tested (HeLa, osteosarcoma, U-amnion) showed extensive cell death, thus indicating that it may have a cytocidal effect on certain tumor cells. It appears that human type II interferon (or a factor present in these preparations) may be a potent antitumor agent.Interferons are classified into two groups, called type I and type II interferons, which differ in their acid stability, their antigenic properties, and the nature of stimulus required for their production (reviewed in refs. 1 and 2). The human fibroblast and leukocyte interferons, so named because of their cellular origins, are both acid stable and are thus classified as type I interferons, although they are antigenically different. On the other hand, the interferon produced by human leukocytes in response to mitogenic or specific antigenic stimuli is acid labile and is classified as type II (or immune) interferon. This type II interferon activity is not neutralized by antisera raised against human fibroblast or leukocyte interferons and therefore appears to be distinct (3, 4).The antiviral action of type I interferons requires the expression of certain cellular genes because it is blocked by inhibitors of either transcription or translation (5-8) or by enucleation of cells (9, 10). Our stu...

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Section: Methodsmentioning

confidence: 99%

Differential efficacies of human type I and type II interferons as antiviral and antiproliferative agents.

Rubin¹,

Gupta²

1980

Proc. Natl. Acad. Sci. U.S.A.

244

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“…These observations led to the investigation and discovery of the inhibitory effect of interferon on granulocytic progenitor cells (CFU-C) [6,13]. Furthermore, the characteristic CGI activity of interferon [6,15] has led to the current interest in a nationwide trial of this agent as an antineoplastic drug.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effects of Human Leukocyte and Fibroblast Interferons on Normal and Chronic Myelogenous Leukemic Granulocytic Progenitor Cells

et al. 1981

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Inhibitory effects of two human interferon preparations, leukocyte interferon (Le-IF) and fibroblast interferon (F-IF), on granulocytic progenitor cells (CFU-C) from hematologically normal cancer patients and from patients with chronic myelogenous leukemia were evaluated. There was a wide variation in sensitivity of CFU-C to both Le-IF and F-IF. F-IF was more inhibitory against CFU-C than Le-IF. Normal CFU-C and chronic myelogenous Leukemia CFU-C were equally inhibited by both interferons. Effects of both interferons were neutralized by corresponding specific antisera but not by the other antisera. These observations confirmed that differences in immunogenicity of the interferons may attend their different origins.

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“…No activity was found in non-small cell lung cancer (Stoopler et al, 1980), but the greater chemosensitivity of small cell lung cancer to other chemotherapeutic agents suggested the need to investigate its responsiveness to interferon. Interferon for clinical studies has usually been derived from human leucocytes (Strander, 1977), but more recently human lymphoblastoid interferon (HLBI) has been available (Priestman, 1980). Monoclonal antibodies may be used to purify interferon (Secher & Burke, 1980;Scott et al, 1982a), and interferon produced by gene cloning is becoming available (Scott et al, 1982b November 1982 used have been variable, but have tended to be up to about 3 megaunits m -2.…”

mentioning

confidence: 99%

Human lymphoblastoid interferon in the treatment of small cell lung cancer

Jones¹,

Bleehen²,

Slater³

et al. 1983

Br J Cancer

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Summary Ten patients with small cell lung cancer were treated with high dose human lymphoblastoid interferon (50-100 megaunitsm-2) for 5 days, followed by low dose interferon (3 megaunits m-2) for 3 weeks. At the end of treatment, and one month later, there was no evidence of either complete or partial response. The treatment produced fever, anorexia and weight loss, with transient leucopenia and thrombocytopenia; there was evidence of a non-cholestatic elevation of serum alanine aminotransferase, with clinical deterioration in the condition of three patients presenting with hyponatraemia. A transient hypocalcaemia during high dose therapy was also noted. It seems that lymphoblastoid interferon as a single agent is unlikely to have a role in the treatment of small cell lung cancer, and that its administration as employed in this study is associated with considerable toxicity.

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Interferons: Anti-neoplastic drugs?

Cited by 135 publications

References 89 publications

Differential efficacies of human type I and type II interferons as antiviral and antiproliferative agents.

Differential efficacies of human type I and type II interferons as antiviral and antiproliferative agents.

Inhibitory Effects of Human Leukocyte and Fibroblast Interferons on Normal and Chronic Myelogenous Leukemic Granulocytic Progenitor Cells

Human lymphoblastoid interferon in the treatment of small cell lung cancer

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