Lecture 26 0503 2012_class

The sensitization phase equivalent to the the primary

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Unformatted text preview: e sensitization phase – equivalent to The the primary immune response the 2. Re-exposure – equivalent to the Re-exposure secondary immune response. It is stronger and faster. stronger Allergic response Allergic Allergic responses Allergic Allergic response Allergic Immediate hypersensitivity reactions are mediated by Immediate antibodies antibodies Delayed hypersensitivity reactions are mediated by Delayed helper T cells and macrophages helper Mast cells are activated by binding of an allergen to IgE Mast antibodies antibodies IgE are produced by B cells and they differ from other antibody IgE isotypes by their predominate location in tissues, where they are tightly bound to mast-cells through IgE receptor tightly Allergies have a strong genetic component Cancer Immunotherapy Outline Outline Antibodies Revisited Cancer Immunotherapy Nonspecific activation Monoclonal antibodies Vaccines Adaptive immunotherapy Rise… Rise… “Magic Bullets” 1980s Optimism: monoclonal antibodies (mAb) Optimism: conjugated with poisons or radiactive isotopes would be targeted to malignant cells and delivery deadly payloads cells Fall… Fall… Infusions of the early monoclonal Infusions antibodies led to immune response antibodies Liver removed the therapeutic mAb before Liver they could reach the target they Resurrection… Resurrection… In 2001 10 mAbs were approved for In human use with applications raging from preventing organ-transplant rejection to treating cancer treating …about 100 more were in clinical trials in about humans humans 2001 Advantages of mAbs Advantages Abs are easier to develop than traditional Abs drugs drugs 1-2 years for an Ab vs. 5 years for a small drug 1-2 molecule molecule $2 million clinical ready Ab $20 million clinical ready small molecule drug Abs are almost never toxic Monoclonal Methods: Classic Monoclonal 1975 Georges Köhler and Cesar Milstein, hler Medical Research Council’’s Laboratory of s Medical Molecular Biology, Cambridge, England Molecular 1984 Nobel Prize in Physiology and 1984 Medicine Medicine Problem with Murine Abs Problem Immune response in patients – HAMA Immune response (human anti-mouse antibodies) response Joint swelling, rashes and kidney failure Solution - Humanization Solution Hybridoma: Human B cells and Immortalized cells Other techniques to produce human mAbs mAbs Transgenic mice Mice are genetically altered to have human antibodies Mice genes genes When the mice are injected with an antig...
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