1. Antibodies, scope of use in medicine 2. What is antibodies? 1. The Ig monomer is a Y -shaped molecule that consists of four polypeptide chains; two…
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  • 1. Antibodies, scope of use in medicine
  • 2. What is antibodies? 1. The Ig monomer is a "Y"-shaped molecule that consists of four polypeptide chains; two identical heavy chains and two identical light chains connected. 2. The variable domain is the most important region for binding to antigens. (Complementarity Determining Regions or idiotypes). 3. The base of the Y plays a role in modulating immune cell activity by bindings various cells receptors.
  • 3. How antibodies work ? As immunoeffectors: 1) Complement-Dependant citotoxicity (CDC): Chelating to antigens and to a specific protein to activate the response. 2) Antibody-Dependant Cell-Mediated Cytoxicity (ADCC): Chelating to antigens and specific cells via cells Fc receptor As bioregulators : 1) Transduction signal inhibited : by ligand capture or chelating ligand protein receptor 2) Transduction signal restored by chelating protein receptor
  • 4. Antibodies evolution in time 1) 1975 – the momab 100% from mice: The Anti-CD3 muromomab/Orthoclone OKT3® is an immunosuppressant drug given to reduce acute rejection in patients with organ transplants. It was the first monoclonal antibody to be approved for clinical use in humans. The CD3 receptor is a membrane protein on the surface of T cells. 2) 1984 – the ximab or chimerized antibodies: Rituximab/Mabthera® or Cétuximab/Erbitux® are far less imunogen apart from Infliximab/Remicade® who get 61% of HAMA. 3) 1988/89 – the zumab or humanized antibodies: Daclizumab/Zenapax® (34% HAHA), Alemtuzumab/MabCampath® (1.9% HAHA) or Transtuzumab/Herceptin® (>0.1% HAHA) 4) 1994-99 – the mumab or fully human antibodies: Panitumumab/Vectibix®
  • 5. Conjugated antibodies • Immunoconjugates or antibodies conjugated to a second molecule : – a toxin – a radioisotope – a label
  • 6. Actual use in cancer (2008)
  • 7. Other developments
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