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1. Introduction
2. Costimulation blockade: bench-to-bedside & back
3. Fifty years of transplantation
4. US transplants by year
5. US organ transplants (N=21,516)
6. Improved short term outcomes
7. Immunosuppression for renal transplantation
8. Activated T cells play central role in rejection
9. Current immunosuppressive agents target T cells
10. Drug target distribution and toxicity
11. Unaffected long term outcomes
12. Costimulation blockade: inadequate results
13. Costimulation: a component of T cell activation
14. Critical costimulatory pathways
15. CD28 signaling
16. Drug toxicity - traditional vs. cosimulation blocking
17. CTLA-4- second receptor for B7 activation antigen
18. CD28 blockade: lessons from early murine studies
19. Transplantation tolerance induced by CTLA4-Ig
20. Rhesus renal allograft model
21. Effect of CTLA4-Ig on renal allograft survival
22. Studies results
23. CTLA4Ig treatment of psoriasis is beneficial
24. CTLA4Ig effective for treatment of RA
25. CD28 blockade: efficacy in humans vs. mice
26. Structural basis for co-stimulation by CTLA-4/B7-2
27. Creation of belatacept (LEA29Y)
28. LEA29Y: more potent co-stimulation blockade
29. LEA29Y renal allograft protocol
30. LEA29Y treatment is beneficial for renal allograft
31. Path to CNI free trials in renal transplantation
32. IM103-100 study: rationale and design
33. The belatacept study group
34. LEA29Y phase II dose-finding study design
35. Study endpoints
36. Primary endpoint: acute rejection
37. Time to onset of acute rejection
38. Summary key secondary endpoints - 12 months
39. Key safety events
40. IM103-100 summary
41. Belatacept/LEA29Y: next steps
42. Costimulation blockade: CD40
43. Costimulatory pathways - CD40 & CD154
44. TNF/TNFR superfamily members
45. X-linked hyper-IgM syndrome
46. CD154: master regulator of T cell responses
47. Anti-CD154 mAbs in transplantation
48. Anti-CD154 in humans
49. Platelet - derived CD154
50. CD40L stabilizes arterial thrombi
51. Targeting CD40: properties of Chi220
52. Islet transplantation in non-human primates
53. LEA29Y/Chi220 islet protocol
54. Prolonged islet allograft survival w/ Chi220/LEA29Y
55. Targeting CD154-CD40 in transplantation
56. Costimulation blockade: summary
57. Summary

Topics Covered

• Clinical transplantation
• Current immunosuppression
• T-cell activation
• Co-stimulatory pathways
• CD28 pathway
• Mechanisms of action and clinical development
• CD40-CD154 pathway

Links

Series:

• Monoclonal Antibodies as Therapeutic Agents

Categories:

• Immunology
• Methods

Therapeutic Areas:

• Immunology & Inflammation

Talk Citation

Larsen, C. (2007, October 1). New strategies to prevent transplant rejection: from molecules to mice to monkeys to man [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved April 20, 2024, from https://hstalks.com/bs/597/.
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Publication History

• Published on October 1, 2007
• Archived on December 10, 2018

Financial Disclosures

• Prof. Christian Larsen has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.