Infergen was launched in the US for the treatment of chronic hepatitis C. The
protein was prepared by examining the sequences of naturally occurring IFN-α's (14
different types) and assigning the most frequently observed amino acid in each
corresponding position. The synthetic DNA coding this consensus peptide of 166
amino acids was ligated into an E. coli expression vector, produced by bacterial cell
fermentation and purified to homogeneity (>98%). lnfergen has 30% identity with
INF-β and 60% identity with IFN-ω. It has the correct disulfide bridges and was
structurally similar to IFN-α. There are three isoforms of IFN's which results in differing
antiviral properties, namely, the extent of NK cell activation, the capacity to induce IL-1, and the presentation of class Ⅰ HLA antigen. lnfergen was more effective than the
other IFN’s with a 10-20 fold greater activity than IFN-α2a and IFN-α2b, had a greater
antiproliferative effect and was more effective at activating NK cells. In addition, it had
immunomodulatory effects similar to IFN-β1b, and IFN-α2a.
일반 설명
IFNs are extremely potent cytokines that possess antiviral,immunomodulating, and antiproliferative actions.IFNsare synthesized by infected cells in response to various inducers and, in turn, elicit either an antiviral statein neighboring cells or a natural killer cell response that destroysthe initially infected cell.With most viruses, the IFNs predominantly inhibit protein synthesis. This takes place through the intermediacy ofIFN-induced proteins such as 2,5-oligoadenylate (2,5-OA) synthetases and a protein kinase, either ofwhich can inhibit viral protein synthesis in the presence ofdouble-stranded RNA. Certain viruses can block the production or activity of selected IFNinducibleproteins and thus counter the IFN effect.IFNs cannot be absorbed orally; to be used therapeutically,they must be given intramuscularly or subcutaneously. Thebiological effects are quite long, so pharmacokinetic parametersare difficult to determine. The antiviral state in peripheralblood mononuclear cells typically peaks 24 hours after a doseof IFN- and IFN-, then decreases to baseline in 6 days.Both recombinant and natural INF- and INF- are approvedfor use in the United States for the treatment of condylomaacuminatum (venereal warts), chronic hepatitis C, chronichepatitis B, Kaposi sarcoma in HIV-infected patients, othermalignancies, and multiple sclerosis.
