A Comparison of Interferon-Con1 with Natural Recombinant Interferons-α: Antiviral, Antiproliferative, and Natural Killer-Inducing Activities

Özeş, Osman N.; Reiter, Zvi; Klein, Susan Blakeley; Blatt, Lawrence M.; Taylor, Milton W.

doi:10.1089/jir.1992.12.55

Cited by 107 publications

(52 citation statements)

References 22 publications

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“…The specific activities of YM643 for VSV and HSV-1 appeared to be lower compared with those in a previous report in which they were 2.5×10 9 to 2×10 10 IU/mg and typically 10-fold more potent than either natural IFNα2a or IFN-α2b (Ozes et al, 1992). Presumably these differences resulted from differences in experimental conditions.…”

Section: Discussioncontrasting

confidence: 69%

Spectrum of Virus Inhibition by Consensus Interferon YM643

Yasuda¹,

Huffman

Smee

et al. 2000

Antivir Chem Chemother

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The spectrum of viruses inhibited by a genetically engineered consensus interferon (IFN) YM643 (interferon alfacon-1) was evaluated using a cytopathic effect inhibition assay or plaque inhibition assay for five DNA viruses and 12 RNA viruses. This activity was compared to that of natural IFN-α derived from Namalwa lymphoblastoid cell line [IFN-α (Namalwa)]. The viruses inhibited by both IFNs were herpesvirus types 1 and 2, human cytomegalovirus, varicella-zoster virus, vesicular stomatitis virus, yellow fever virus, bovine viral diarrhoea virus, Semliki Forest virus, western equine encephalitis virus, encephalomyocarditis virus, rhinovirus type A, respiratory syncytial virus, Newcastle disease virus and influenza virus type A (H1N1). Neither IFN inhibited coxsackie virus B1, reovirus type 3 or vaccinia virus in the experimental conditions used. The specific activity of YM643 in human cells generally ranged from 3.6¥10 7 to 2.1¥10 9 IU/mg, which was greater than that of IFN-a (Namalwa), which ranged from 3.1¥10 6 to 4.6¥10 8 IU/mg against all sensitive viruses, except human cytomegalovirus and rhinovirus type 1A, which displayed approximately equal sensitivity to both IFNs. Significantly, the potency of YM643 against bovine viral diarrhoea virus and yellow fever virus, which were selected to serve as surrogates of hepatitis C virus, equalled or exceeded that of IFN-a (Namalwa). These results suggest that the genetically engineered YM643 is more potent than natural IFN-a.

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Section: Discussioncontrasting

confidence: 69%

Spectrum of Virus Inhibition by Consensus Interferon YM643

Yasuda¹,

Huffman

Smee

et al. 2000

Antivir Chem Chemother

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“…We have not addressed the role of IFN-␣ subtypes other than that of IFN-␣2a (and the allelic variant IFN-␣2b, which yielded similar results; data not shown) in the current study. The results reported here warrant a similar evaluation of other IFN-␣ subtypes, as well as the consensus IFN-␣ (IFN-con1 or CIFN), which has significant antiviral activity against VSV (63,64). This information will facilitate the design of OV therapies with enhanced selectivity for tumor cells.…”

Section: Discussionsupporting

confidence: 58%

Interferon Beta and Interferon Alpha 2a Differentially Protect Head and Neck Cancer Cells from Vesicular Stomatitis Virus-Induced Oncolysis

Westcott

Liu

Rajani

et al. 2015

J Virol

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Oncolytic viruses (OV IMPORTANCEThere has been a great deal of progress in the development of oncolytic viruses. However, a major problem is that individual cancers vary in their sensitivity to oncolytic viruses. In many cases this is due to differences in their production and response to interferons (IFNs). The experiments described here compared the responses of head and neck squamous cell carcinoma cell lines to two IFN subtypes, IFN-␣2a and IFN-␤, in protection from oncolytic vesicular stomatitis virus. We found that IFN-␣2a was significantly less protective for cancer cells than was IFN-␤, whereas normal cells were equivalently protected by both IFNs. These results suggest that from a therapeutic standpoint, selectivity for cancer versus normal cells may be enhanced by pairing VSV with IFN-␣2a. T he use of viruses to selectively kill cancer cells (oncolytic virotherapy) is a promising alternative therapy for cancer (1). The basis for this treatment approach is that cancer cells frequently have defective antiviral responses that develop as a consequence of cellular transformation (2-5). As a result, they are more susceptible than their normal cellular counterparts to infection and apoptotic death induced by cytopathic viruses (6, 7). Vesicular stomatitis virus (VSV), a negative-strand RNA virus of the family Rhabdoviridae, is being investigated as an oncolytic agent for the treatment of prostate (6, 8), skin (9, 10), colorectal (2, 11, 12), pancreatic (13), brain (14, 15), and other cancers. A variety of attenuated VSV strains have been engineered to express heterologous genes to increase selectivity for tumor cells, to augment tumor cell killing, or to enhance antitumor immunity (reviewed in reference 16). Recombinant VSV strains have produced encouraging preclinical results for a broad range of tumor types (17-22), and VSV expressing the human beta interferon (IFN-␤) gene currently is undergoing a phase I clinical trial for the treatment of hepatocellular carcinoma (http://www.clinicaltrials.gov/ct2/show /study/NCT01628640).Because normal cells respond to viral infection by mounting a protective type I IFN response while many cancer cells do not share this capability (7), the selectivity of VSV for cancer cells has been improved by combination treatment with type I IFN, for example, by incorporating the gene for IFN-␤ into the VSV genome or by the use of mutant or engineered VSV strains that induce robust IFN production (2, 6, 18). Wild-type VSV inhibits host antiviral responses by globally suppressing host-directed gene expression due to the activity of the viral matrix (M) protein (2,(23)(24)(25). M protein mutant strains of VSV, such as M51R VSV, are severely defective for inhibition of the host antiviral response

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“…This IFN is an artificial cytokine that contains the most common amino acid at each position in the protein among all human IFN-a subtypes (Blatt et al, 1996). In vitro studies demonstrated a higher anti-viral activity against vesicular stomatitis virus (VSV) of CIFN compared with IFN-a2a or 2b (Ozes et al, 1992). Clinical studies with therapy-naive chronic HCV patients treated with CIFN plus ribavirin showed more SVR than with standard treatment (reviewed in Witthoft 2008) .…”

Section: New Ifnsmentioning

confidence: 99%

IFN‐α subtypes: distinct biological activities in anti‐viral therapy

Gibbert

Schlaak

Yang

et al. 2013

British J Pharmacology

152

138

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During most viral infections, the immediate host response is characterized by an induction of type I IFN. These cytokines have various biological activities, including anti‐viral, anti‐proliferative and immunomodulatory effects. After induction, they bind to their IFN‐α/β receptor, which leads to downstream signalling resulting in the expression of numerous different IFN‐stimulated genes. These genes encode anti‐viral proteins that directly inhibit viral replication as well as modulate immune function. Thus, the induction of type I IFN is a very powerful tool for the host to fight virus infections. Many viruses evade this response by various strategies like the direct suppression of IFN induction or inhibition of the IFN signalling pathway. Therefore, the therapeutic application of exogenous type I IFN or molecules that induce strong IFN responses should be of great potential for future immunotherapies against viral infections. Type I IFN is currently used as a treatment in chronic hepatitis B and C virus infection, but as yet is not widely utilized for other viral infections. One reason for this restricted clinical use is that type I IFN belongs to a multigene family that includes 13 different IFN‐α subtypes and IFN‐β, whose individual anti‐viral and immunomodulatory properties have so far not been investigated in detail to improve IFN therapy against viral infections in humans. In this review, we summarize the recent achievements in defining the distinct biological functions of type I IFN subtypes in cell culture and in animal models of viral infection as well as their clinical usage in chronic hepatitis virus infections.

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A Comparison of Interferon-Con1 with Natural Recombinant Interferons-α: Antiviral, Antiproliferative, and Natural Killer-Inducing Activities

Cited by 107 publications

References 22 publications

Spectrum of Virus Inhibition by Consensus Interferon YM643

Spectrum of Virus Inhibition by Consensus Interferon YM643

Interferon Beta and Interferon Alpha 2a Differentially Protect Head and Neck Cancer Cells from Vesicular Stomatitis Virus-Induced Oncolysis

IFN‐α subtypes: distinct biological activities in anti‐viral therapy

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