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Printable Handouts
Navigable Slide Index
- Introduction
- Costimulation blockade: bench-to-bedside & back
- Fifty years of transplantation
- US transplants by year
- US organ transplants (N=21,516)
- Improved short term outcomes
- Immunosuppression for renal transplantation
- Activated T cells play central role in rejection
- Current immunosuppressive agents target T cells
- Drug target distribution and toxicity
- Unaffected long term outcomes
- Costimulation blockade: inadequate results
- Costimulation: a component of T cell activation
- Critical costimulatory pathways
- CD28 signaling
- Drug toxicity - traditional vs. cosimulation blocking
- CTLA-4- second receptor for B7 activation antigen
- CD28 blockade: lessons from early murine studies
- Transplantation tolerance induced by CTLA4-Ig
- Rhesus renal allograft model
- Effect of CTLA4-Ig on renal allograft survival
- Studies results
- CTLA4Ig treatment of psoriasis is beneficial
- CTLA4Ig effective for treatment of RA
- CD28 blockade: efficacy in humans vs. mice
- Structural basis for co-stimulation by CTLA-4/B7-2
- Creation of belatacept (LEA29Y)
- LEA29Y: more potent co-stimulation blockade
- LEA29Y renal allograft protocol
- LEA29Y treatment is beneficial for renal allograft
- Path to CNI free trials in renal transplantation
- IM103-100 study: rationale and design
- The belatacept study group
- LEA29Y phase II dose-finding study design
- Study endpoints
- Primary endpoint: acute rejection
- Time to onset of acute rejection
- Summary key secondary endpoints - 12 months
- Key safety events
- IM103-100 summary
- Belatacept/LEA29Y: next steps
- Costimulation blockade: CD40
- Costimulatory pathways - CD40 & CD154
- TNF/TNFR superfamily members
- X-linked hyper-IgM syndrome
- CD154: master regulator of T cell responses
- Anti-CD154 mAbs in transplantation
- Anti-CD154 in humans
- Platelet - derived CD154
- CD40L stabilizes arterial thrombi
- Targeting CD40: properties of Chi220
- Islet transplantation in non-human primates
- LEA29Y/Chi220 islet protocol
- Prolonged islet allograft survival w/ Chi220/LEA29Y
- Targeting CD154-CD40 in transplantation
- Costimulation blockade: summary
- 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:
Categories:
Therapeutic Areas:
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 December 3, 2024, from https://doi.org/10.69645/OWTW7371.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Christian Larsen has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
New strategies to prevent transplant rejection: from molecules to mice to monkeys to man
A selection of talks on Immunology & Inflammation
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