Lecture 26 0503 2012_class

Antigen they when produce human antibodies produce

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Unformatted text preview: en they When produce human antibodies produce Antibodies Phage Display Phage Display Method Method Transgenic mice and Phage display methods methods Emerging Trends Transgenic mammals that secrete mAbs in Transgenic their milk their Centocor and Johnson & Johnson – transgenic goats Infigen – transgenic cows Transgenic plants Epicyte and Dow – corn plants that are able to Epicyte generate mAbs generate Activation of the Immune System Activation 1800s – physicians noticed that tumors 1800s sometimes regressed in cancer patients who contracted bacterial infection contracted 1892 – 1936 – William Coley, a surgeon at the 1892 Memorial Hospital in New York City infected cancer patients with bacteria and devised a vaccine consisting of killed bacteria to initiate a tumor-killing response. The results were very unpredictable. unpredictable 1970s and 1980s – using cytokines to activate 1970s the immune system. Relatively few patients benefit from this approach alone. benefit Cancer Antigens Cancer Hypothesis: cancer cells might display Hypothesis: molecules that signaled their abnormality molecules Tumor rejection antigens: point mutations mutations TRAs: unmutated proteins TRAs: Monoclonal Antibodies Monoclonal Monoclonal Abs have revealed a large array of antigens Monoclonal that exist on human cancer cells that Virtually all these antigens are also found on normal Virtually cells cells Is antibody based therapy hopeless? Is There are opportunities: The antigen in normal tissues may not be accessible The to blood-borne Abs to The cancer cells may (and they very often do) The express more antigens than normal cells express Ab-induced injury of normal cells may be reversible MAbs Strategies MAbs Abs themselves destroy cancer cells Inflammatory reaction that destroys tissues at the tumor site Blocking pathways that are important for survival – HER2 Blocking signaling signaling Abs as delivery vehicles for tumor-killing agents Radiactive isotopes Toxins Chemotherapeutic drugs Enzymes Genetic therapy MAbs Evaluation MAbs Criterion: a therapeutic Ab should Criterion: be taken by tumor in significantly greater amounts than by normal tissue tissue Studies of biodistribution using Studies radioactive isotopes radioactive A33 story – mAbs for colon A33 cancer cancer 1982 – the antigen was identified 1988 – first clinical study 1991 – the start of the therapeutic trials 1995 – the first patients injected with the 1995 humanized antibody h...
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