3. Most active research area for cancer treatment Hundreds protocols are in clinic trials Why tumor Bio-therapy? Current anti-tumor therapy used in Clinic: Surgery: primary tumor, No metastases Radiation : surface, small and localized tumors Chemotherapy: liquid tumor, metastases Tumor Bio-therapy
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6. Gene Therapy: A Brief History Jesse Gelsinger , 1999 Ashanti de Silva , 1990 Alain Fischer , 2003 1990 Ashanti de Silva , USA (ADA 所致联合免疫缺陷) 1999 Jesse Gelsinger , USA 2003 Alain Fischer , France 2003 Adrian Thrasher , UK
11. Target - specificity The problem with Gene therapy is mainly due to vector (immunogenic and low specificity for tumor)
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13. The elimination phase of Cancer Immunoediting Dunn et al, Nature Immunology, 2002; 3:991
14. Effective immune responses eliminate tumor Tumors must escape from immune recognition Dunn et al, Nature Immunology, 2002; 3:991
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16. Tumor Vaccine ( treatment, not prevention) Cell based vaccine: Best and most widely used so far tumor cell based vaccine: hard to get enough cells; DC ( 树突状细胞) based vaccine widely used in clinic
24. Adaptive immune responses can be divided into two related activities—recognition and response . require co-operation between Lymphocytes and Ag presenting cell (APC, 抗原递呈细胞 )
29. 危险? 自己人? 抗原 处理抗原 摄取抗原 S1 S2 效应细胞 APC 免疫应答 APC 双信号 ? Can we use adjuvant ( 佐剂) to activate APC, (increase the co-stimulatory signals), during the Ag loading?
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33. Get more “fighter”? culture immune cells in vitro ( >10 10 ) Problem: functional activity? Reach the tumor?
34. In vivo, only high affinity CD8+ CTL can response to low levels of Tumor Ag, proliferate, and provide protective immunity; Generation of these CTL dependent on the expression of co-stimulatory molecules on DC Thus , effective loading of tumor Ag, helping the maturation and expression of co-stimulatory molecules on DC simultaneously ( 同时) are the dreams of tumor-immunologists.