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Recombinant DNA in Medicine Industry- Monoclonal Antibodies

Recombinant DNA in Medicine Industry- Monoclonal Antibodies. Topics in Nanobiotechnology- April 2004- Maria Viviana Duarte. As soon as first successful cloning experiments were reported in 1973, applications for this powerful technology quickly followed-

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Recombinant DNA in Medicine Industry- Monoclonal Antibodies

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  1. Recombinant DNA in Medicine Industry- Monoclonal Antibodies Topics in Nanobiotechnology- April 2004- Maria Viviana Duarte

  2. As soon as first successful cloning experiments were reported in 1973, applications for this powerful technology quickly followed- Proteins were produced through recombinant DNA technology for : Introduction • Somatostatin (1976)- 14 aminoacids peptide neurtransmitter • *Treatment of numerous diseases • Insulin for the treatment of diabetes • Human Growth Hormone • Food Production • MAb development • etc Topics in Nanobiotechnology- April 2004- Maria Viviana Duarte

  3. Expression Systems are developed to Produce Recombinant Proteins Cloning the gene or cDNA encoding a particular proteins is only the first of many steps needed to produce a recombinant protein Next step: put he gene into a host cell for production Topics in Nanobiotechnology- April 2004- Maria Viviana Duarte

  4. Expression Systems The choice of which cell is used dependes on the project goal and on the properties of the protein to be produced Topics in Nanobiotechnology- April 2004- Maria Viviana Duarte

  5. Major limitation in the therapeutic use of antibodies Monoclonal Antibodies Function • Antibodies are exquisitely selective proteins that can bind to a single target among millions of irrelevant sites • Could effectively seek and destroy tumor cells and infectious agents wherever the reside Producing a useful antibody in large quantities Topics in Nanobiotechnology- April 2004- Maria Viviana Duarte

  6. Reserchers tested myelomas Development of monoclonal antibody technology Researchers tested myelomas Lack to produce an antibody to their specifications Hybridoma- produce antibodies specified by the lymphocyte from the immunized animal • Monoclonal antibodies are already widely used for the diagnostic of infections and cancer and for the imaging of tumors for radiotherapy • Preparing specfic antibodies: abzyme- antibodies with catalytic activity, birecognition, etc Topics in Nanobiotechnology- April 2004- Maria Viviana Duarte

  7. Hybridoma Recombinant DNA- Watson, Gilman, Witkowski, Zoller. Scientific American Books. 1992 Topics in Nanobiotechnology- April 2004- Maria Viviana Duarte

  8. Bypassing fusion step Direct cloning antibody cDNAs from the lymphocytes of immunized mice Recombinant DNA- Watson, Gilman, Witkowski, Zoller. Scientific American Books. 1992 Topics in Nanobiotechnology- April 2004- Maria Viviana Duarte

  9. More Monoclonal antibodyes • Humanized MAb • Bispecific antibodies • Effector Domains modification Topics in Nanobiotechnology- April 2004- Maria Viviana Duarte

  10. Monoclonal antibodies Usually mouse protein What about this foreing proteins in human system? More Monoclonal antibodyes- Humanized Humanized monoclonal antibodies Topics in Nanobiotechnology- April 2004- Maria Viviana Duarte

  11. First method: encoded proteins in which the variable regions from the mouse antibody were fused the constant regions from a human antibody The variable regions differ in sequence from on antiblody to another, this is the region of the protein that binds the antigen Humanized monoclonal antibodies How to humanized the MAb? Not fully humanized Recombinant DNA- Watson, Gilman, Witkowski, Zoller. Scientific American Books. 1992 Topics in Nanobiotechnology- April 2004- Maria Viviana Duarte

  12. Few of the hundred aminoacids in Variable region contact the antigen (complementary determining regions CDRs) Just CDR to be transferred Humanized monoclonal antibodies Humanized MAb in clinical trials as an immunosuppressant and for treatment of lymphoid tumors. Topics in Nanobiotechnology- April 2004- Maria Viviana Duarte

  13. Humanized monoclonal antibodies Review article Supported by a grant from Zeneca Pharmaceuticals Humanized antibodies as potential therapeutic drugs Surender K Vaswani, MD and Robert G Hamilton, PhD Topics in Nanobiotechnology- April 2004- Maria Viviana Duarte

  14. Humanized monoclonal antibodies Topics in Nanobiotechnology- April 2004- Maria Viviana Duarte

  15. Bispecific antibodies Bispecific antibodies in cancer therapy.Segal DM, Weiner GJ, Weiner LM.Immune Targeting Section, Experimental Immunology Branch, National Cancer Institute, Building 10 Room 4B36, National Institutes of Health, Bethesda, MD 20892-1360, USA. dave_segal@nih.govBased upon in vitro and animal studies, a number of Phase I and II clinical trials have been initiated to test whether bispecific antibodies could redirect immune effectors against tumor cells in cancer patients. Recently, results from those trials showed beneficial effects in some patients but it is clear many problems remain to be solved. In addition, molecular engineering approaches are providing new and improved sources of clinically relevant bispecific antibodies. http://users.telenet.be/nmertens/U11/IM_bispecific_antibodies.htm Topics in Nanobiotechnology- April 2004- Maria Viviana Duarte

  16. Thanks for your attention Topics in Nanobiotechnology- April 2004- Maria Viviana Duarte

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