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Tumor  Biotherapy  肿瘤生物治疗 Limin Zheng E-mail: zhenglm@mail.sysu.edu.cn
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],DeVita   Cancer:  Principles and Practice of Oncology Part IV:  Newer Approaches in Cancer Treatment (most of them are tumor biotherapy)
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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Tumor Bio-therapy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
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
Gene Therapy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Obstacles in Gene Therapy - vector ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
High immunogenecity of vector 载体免疫原性强和靶向性差 Immunogenecity of Adenovirus Adenovirus
Target - specificity The problem with Gene therapy is mainly due to  vector (immunogenic and low specificity for tumor)
Tumor Bio-therapy ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
The elimination phase of Cancer Immunoediting Dunn et al,  Nature Immunology, 2002; 3:991
Effective immune responses eliminate tumor Tumors must escape from immune recognition Dunn et al,  Nature Immunology, 2002; 3:991
[object Object],[object Object],[object Object],[object Object],[object Object]
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
Anti-tumor effector arms of the immune response
Tumor vaccines: Use Dendritic cells, the most powerful APC, to elicit anti-tumor immune responses DC DC Tc
Interaction between DC and lymphocytes
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Ex vivo  loading of DC with tumor Ag
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[object Object],[object Object],[object Object]
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 )
Activation of T cells by dendritic cells
 
 
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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?
 
 
Tumor Vaccine :   Limited success obtained in clinic, more challenges remain ,[object Object],[object Object],[object Object],[object Object]
Get more “fighter”? culture immune cells in vitro ( >10 10 ) Problem:  functional activity? Reach the tumor?
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.
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
篦麻毒素
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Cancer immunotherapy: moving beyond current vaccines NATURE MEDICINE  2004 , 10 : 909-915 ,[object Object],[object Object]
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5 tumor biotherapy

  • 1. Tumor Biotherapy 肿瘤生物治疗 Limin Zheng E-mail: zhenglm@mail.sysu.edu.cn
  • 2.
  • 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
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  • 10. High immunogenecity of vector 载体免疫原性强和靶向性差 Immunogenecity of Adenovirus Adenovirus
  • 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
  • 17. Anti-tumor effector arms of the immune response
  • 18. Tumor vaccines: Use Dendritic cells, the most powerful APC, to elicit anti-tumor immune responses DC DC Tc
  • 19. Interaction between DC and lymphocytes
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  • 21. Ex vivo loading of DC with tumor Ag
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  • 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 )
  • 25. Activation of T cells by dendritic cells
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  • 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.
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