GKA deel 1 college 10

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GKA deel 1 college 10

  1. 2. Immunotherapy for cancer: Terminologie M. Old, Sci Am 275-3, 1996
  2. 3. Immunotherapy for cancer: Terminologie M. Old, Sci Am 275-3, 1996 <ul><li>Antigeen: induceert een immuunrespons </li></ul><ul><ul><li>Antilichaam of cytotoxische T-cel </li></ul></ul><ul><li>Antilichaam (Ab) </li></ul><ul><ul><li>Herkent een antigeen (Ag) </li></ul></ul><ul><ul><li>Bindt aan epitoop </li></ul></ul><ul><li>Elke cel (met een kern) produceert peptiden van gemaakte eiwitten aan buitenkant van de cel in een receptorcomplex </li></ul><ul><ul><li>MHC: major histocompatibiliteitscomplex </li></ul></ul><ul><li>Cytokines </li></ul><ul><ul><li>Stimuleren of remmen immuunsysteem </li></ul></ul><ul><ul><li>Interferon, interleukines, TNF  </li></ul></ul><ul><li>Macrofagen, dendritische cellen </li></ul><ul><ul><li>Endocyterende witte bloedcellen </li></ul></ul><ul><li>Complement </li></ul><ul><ul><li>Activeerbaar systeem van proteases in bloed die Ag-Ab of cel-Ab complexen herkennen en afbreken </li></ul></ul>
  3. 4. Immunotherapy for cancer Old, Sci Am 275-3, 1996
  4. 5. Immunotherapy for cancer Old, Sci Am 275-3, 1996 BCG: Bacillus Calmette-Guérin tuberculose vaccin
  5. 6. Immunotherapy for cancer Old, Sci Am 275-3, 1996 BCG: Bacillus Calmette-Guérin tuberculose vaccin +/- 1975
  6. 7. Immunotherapy for cancer Old, Sci Am 275-3, 1996 BCG: Bacillus Calmette-Guérin tuberculose vaccin Immunesurveillance: the immune system seeks and destroys emerging cancer cells; failure causes cancer +/- 1975
  7. 8. Immunotherapy for cancer: Terminologie M. Old, Sci Am 275-3, 1996 <ul><li>Antigeen: induceert een immuunrespons </li></ul><ul><ul><li>Antilichaam of cytotoxische T-cel </li></ul></ul><ul><li>Antilichaam (Ab) </li></ul><ul><ul><li>Herkent een antigeen (Ag) </li></ul></ul><ul><ul><li>Bindt aan epitoop </li></ul></ul><ul><li>Elke cel (met een kern) produceert peptiden van gemaakte eiwitten aan buitenkant van de cel in een receptorcomplex </li></ul><ul><ul><li>MHC: major histocompatibiliteitscomplex </li></ul></ul><ul><li>Cytokines </li></ul><ul><ul><li>Stimuleren of remmen immuunsysteem </li></ul></ul><ul><ul><li>Interferon, interleukines, TNF  </li></ul></ul><ul><li>Macrofagen, dendritische cellen </li></ul><ul><ul><li>Endocyterende witte bloedcellen </li></ul></ul><ul><li>Complement </li></ul><ul><ul><li>Activeerbaar systeem van proteases in bloed die Ag-Ab of cel-Ab complexen herkennen en afbreken </li></ul></ul>
  8. 9. Immunotherapy for cancer Old, Sci Am 275-3, 1996 BCG: Bacillus Calmette-Guérin tuberculose vaccin Immunesurveillance: the immune system seeks and destroys emerging cancer cells; failure causes cancer +/- 1975
  9. 10. Immunotherapy for cancer Old, Sci Am 275-3, 1996
  10. 11. Immunotherapy for cancer Old, Sci Am 275-3, 1996
  11. 12. Immunotherapy for cancer Old, Sci Am 275-3, 1996
  12. 13. Immunotherapy for cancer Old, Sci Am 275-3, 1996 Humaniseren!= Ab gene- tisch zo veranderen dat muis vervangen wordt door menselijk Ab
  13. 14. Immunotherapy for cancer Old, Sci Am 275-3, 1996 Humaniseren!= Ab gene- tisch zo veranderen dat muis vervangen wordt door menselijk Ab
  14. 15. Monoclonal antibodies Köhler en Milstein 1975 <ul><li>Immuniseer muis met Ag </li></ul><ul><li>Isolatie B-cellen uit milt </li></ul><ul><li>Fuseer B-cellen met myeloma cel: </li></ul><ul><ul><li>Gefuseerde cel produceert Ab en reproduceert onbeperkt </li></ul></ul><ul><li>Elke B-cel produceert één type Ab </li></ul><ul><ul><li>Monoklonaal </li></ul></ul>
  15. 16. Immunotherapy for cancer Old, Sci Am 275-3, 1996
  16. 17. Immunotherapy for cancer Old, Sci Am 275-3, 1996 Mouse T-cells from tumor can protect another mouse
  17. 18. Immunotherapy for cancer Old, Sci Am 275-3, 1996
  18. 19. Summary sofar Old, Sci Am 275-3, 1996 <ul><li>Non-specific immunotherapy </li></ul><ul><ul><li>BCG: bacillus Calmette-Guerin (tuberculose vaccin) </li></ul></ul><ul><ul><li>Adjuvantia, zoals Alum </li></ul></ul><ul><li>Passive immunotherapy </li></ul><ul><ul><li>Antibody-based therapy </li></ul></ul><ul><li>Active immunotherapy </li></ul><ul><ul><li>Vaccine-based </li></ul></ul><ul><li>Adoptive immunotherapy </li></ul><ul><ul><li>Stimulate patient’s T-cells in vitro with tumorcell or Ag </li></ul></ul>
  19. 20. Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes <ul><li>Science 2006, 314: 126-129 </li></ul><ul><li>R.A. Morgan, M.E. Dudley, J.R. Wunderlich, M.S. Hughes,.J.C. Yang, R.M. Sherry, R.E. Royal, S.L. Topalian, U.S. Kammula, N.P. Restifo, Z. Zheng, A. Nahvi, C.R. de Vries, L.J. Rogers-Freezer, S.A. Mavroukakis, S.A. Rosenberg </li></ul>Liver metastasis
  20. 21. Summary sofar Old, Sci Am 275-3, 1996 <ul><li>Non-specific immunotherapy </li></ul><ul><ul><li>BCG: bacillus Calmette-Guerin (tuberculose vaccin) </li></ul></ul><ul><ul><li>Adjuvantia, zoals Alum </li></ul></ul><ul><li>Passive immunotherapy </li></ul><ul><ul><li>Antibody-based therapy </li></ul></ul><ul><li>Active immunotherapy </li></ul><ul><ul><li>Vaccine-based </li></ul></ul><ul><li>Adoptive immunotherapy </li></ul><ul><ul><li>Stimulate patient’s T-cells in vitro with tumorcell or Ag </li></ul></ul>
  21. 22. Treatment result of rituximab Old, Sci Am 275-3, 1996 Lungs
  22. 23. Categories of cancer vaccines Old, Sci Am 275-3, 1996
  23. 24. Categories of cancer vaccines Old, Sci Am 275-3, 1996 M.E. Dudley et al., Science 2002, 298:850-854 Cancer Regression and Autoimmunity in Patients After Clonal Repopulation with Antitumor Lymphocytes
  24. 25. Hoe verstopt de tumorcel zich voor het immuunsysteem? Old, Sci Am 275-3, 1996 <ul><li>Veranderen van karakteristieken </li></ul><ul><ul><li>MHC </li></ul></ul><ul><ul><li>Tumor antigens </li></ul></ul><ul><li>Onderdrukken van immuunsysteem </li></ul><ul><ul><li>Tumor produceert TGF-ß </li></ul></ul><ul><ul><li>Bestraling! </li></ul></ul><ul><ul><li>Medicijnen </li></ul></ul><ul><li>Verstoppen voor immuunsysteem </li></ul><ul><ul><li>Hersenen </li></ul></ul><ul><ul><li>Bindweefsel </li></ul></ul><ul><li>Snelle groei </li></ul><ul><ul><li>Immuunsysteem te langzaam </li></ul></ul>
  25. 26. Monoclonal antibodies as medicin Old, Sci Am 275-3, 1996 <ul><li>Herceptin (trastuzumab) </li></ul><ul><ul><li>Humanised </li></ul></ul><ul><ul><li>HER2 GF receptor </li></ul></ul><ul><li>Rituxan (rituximab) </li></ul><ul><ul><li>CD20 receptor of B lymphocytes </li></ul></ul>==================

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