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    Home > Biochemistry News > Biotechnology News > Phage display technology and antibody drug development will settle the dust.

    Phage display technology and antibody drug development will settle the dust.

    • Last Update: 2020-08-07
    • Source: Internet
    • Author: User
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    The 2018 Nobel Prize in Chemistry has been awarded to Frances Arnold, George Smith and Gregory Winter.
    half of the chemistry prize went to American scientist Frances Arnold for her work in the targeted evolution of enzymes, and the other half went to British scientist Gregory Winter and American scientist George Smith for their great achievements in the bacteriophage display of peptides and antibodies.
    the development of science and technology is the driving force of drug research and development, Smith and others developed phage display technology, so that antibody drug research and development has a breakthrough.
    phage display technology has become one of the most important drug screening platforms, it can be used not only for peptide, monoantiphoresis screening, but also for other protein screening, the diversity of screening is also one of the highlights of the technology.
    So, what is phage demonstration technology? The technology was developed by Smith in 1985, and Winter has since developed it, using a genetically engineered phage, a virus that infects bacteria as a host.
    A. Genetic engineering inserts DNA sequences encoded in polypeptides or protein libraries into the shell protein genes of the phage so that peptides or proteins can be expressed on the surface of the phage;
    1. Capture the phages of specifically bound target proteins with a culture plate with fixed target proteins; 2. Wash the phages that are not bound to the target; 3 will wash off the phages that bind to the target for the next round of transformation; 4. Carry out the next round of infection and transformation; and 5. further enlarge the number of target phages.
    so, the cycle goes back and forth to get the desired high affinity antibody.
    , what good is it? First, not all protein pheletos expressed in the library are useful, so that the epitopes of interest can be screened to ensure the best activity of the candidate drug, and second, in vitro experiments, human and non-human targets can be screened, which saves time in preclinical trials.
    wash away the epitope that is not fully bound to the target, leaving only the most affinity-related position.
    at present, a variety of antibody drugs have been successfully marketed using this technology, Adalimumab monotomoab is one of the best examples, the successful development of the first all-human recombinant IgG1: monoclonal antibodies, the drug has been the top of the best-selling drugs in recent years, in 2017, its sales of $18.4 billion.
    in addition, there are several drugs that use the technology have been successfully marketed, and a number of drugs to be marketed are in clinical trials.
    let us know about these successful lying drugs.
    Adalimumab Adalimumab is an all-human recombinant IgG1-sac monoclonal antibody, the first approved anti-tumor necrosis factor TNF alpha drug for the treatment of rheumatoid arthritis, which was introduced in the United States in 2002.
    Adalimumab was screened using "guidance choices" using phage demonstration techniques.
    this step is divided into two steps, first the researchers developed the rat-derived anti-human TNF antibody MAK195, but the rat-source antibodies can not be used as an autoimmune disease drug, so they used this rat-source antibody to guide the separation of the same epitopus as MAK195 human-derived antibodies.
    used THE heavy and light chains of MAK195 to find the matching human DNA sequence in the protein bank, and then used phage demonstration techniques for further screening to obtain high affinity anti-TNF antibodies.
    this creates the Adalimumab single resistance.
    Belimumab Belimumab is a human source IgG1 monoclonal antibody. The
    , developed by Cambridge Antibody Technology in conjunction with GlaxoSmithKline, was approved for the treatment of systemic lupus in 2011 and is the first targeted drug for the treatment of systemic lupus in more than 50 years.
    Belimumab binds to B lymphocyte stimulator (BLyS) to prevent BLyS from binding to B lymphocytes and promotes apoptosis.
    researchers screened 1,200 antibodies using single-stranded variable fragment (scFv) phage display to get a high affinity belimumab, a drug that preclinical studies have shown inhibits B lymphocyte growth in crab-eating macaques.
    clinical trials have shown that Belimumab can be effective in improving patients' conditions.
    Ranibizumab (Lucentis? Ranibizumab was developed by Genentech to bind to VEGF-A and inhibit its activity in antigen binding fragments (Fab).
    rat-derived antibody A4.6.1 was well used in mouse tumor models and the anti-tumor drug Bevacizumab (Avastin?) was obtained. ), Ranibizumab is also a candidate compound for a mutation site in A4.6.1.
    Clone Y0317 (i.e. Ranibizumab) has a affinity of 0.1nM for VEGF-A, contains only 6 mutations that differ from parental, and increases the affinity of VEGF by more than 100 times, greatly reducing the dose of the drug.
    the drug was approved for the treatment of age-related macular degeneration in 2006, for the treatment of diabetic macular edema in 2010 and for the treatment of diabetic retinopathy in 2015.
    Ecallantide?? Ecanllantide is made up of 60 amino acids and is a recombinant peptide-releasing enzyme protein inhibitor.
    found Ecallantide as a stent using the first Kunitz-D1 library of human lipoprotein-related clotting inhibitors (LACI-D1).
    approved for the drug in 2009 for the treatment of hereditary vascular edema (HAE), a rare genetic disorder.
    Romiplostim (Nplate?) Romiplostim contains two identical subunits, each consisting of an IgG1 Fc structure and a c-Mpl binding region, combined with platelet-producing receptors (TPOR), approved by the U.S. FDA in 2008 and is the first FDA-approved peptide-producing drug, the first and the first and only platelet-producing drug.
    Raxibacumab (Abthrax?? Raxibacumab is a human-derived monoclonal IgG1 antibody that is used to treat and prevent diseases caused by Bacillus anthrax infection, and Raxibacumab combines the protective antigens of Bacillus anthrax to prevent the release of bacterial toxins.
    the drug, developed by Human Genome Sciences, has shown that Raxibacumab significantly increases the survival of rabbits and monkeys.
    Necitumab?? Necitumumab was developed by ImClone Systems, Eli Lilly and Bristol-Myers Squibb, a technology library of "de Haard" Dya Fabx phage demonstrations, which target epidermal growth factor receptors (EGFR).
    in the development of the drug, epidermal-like cancer cells were targeted for antibody screening, and Necitumumab's affinity for the cell was 3.3 to 0.5nM.
    2015, Necitumumab was approved for listing, in conjunction with gemcitabine and cisplatin to treat squamous non-small cell lung cancer.
    Ramuirumab (Cyramza? Ramucirumab is also screened from the deHaard Fab Phage Display Technology Library, VEGFR2 drug, Ramucirumab is a library of human Fab non-immune phage display technology, which is amplified through PCR to increase the human source heavy and light chains.
    in preclinical studies, the drug showed excellent anti-tumor activity, in clinical III trials showed that the drug on a variety of tumors have significant inhibition effect.
    approved by the U.S. FDA in 2014 for the treatment of advanced stomach cancer or gastric esophagus binding adenocarcinoma.
    concluded that in addition to the listed drugs described above, many more drugs are in clinical trials.
    in antibody drug and protein drug screening, phage display technology shows great superiority, improves the success rate of drug research and development, but also saves the time and cost of drug screening.
    (biovalleybioon.com) Source: Supplied.
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