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Updated: May 24, 2026
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Heterotopic Auxiliary Whole Liver Rat Transplant Model Utilizing a Hepaticoureterostomy for Allograft Rejection Studies
Published on: March 8, 2024
Long-term hepatic allograft acceptance based on CD40 blockade by ASKP1240 in nonhuman primates
T Oura1, K Yamashita, T Suzuki
1Department of General Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Summary
Blocking CD40 with ASKP1240 antibody shows promise for liver transplantation. A six-month treatment prevented rejection in nonhuman primates without serious side effects, suggesting its potential as an immunosuppressant.
Area of Science:
- Immunology
- Transplantation Biology
- Drug Development
Background:
- CD40-CD154 pathway blockade is a key immunosuppression strategy for organ transplantation.
- Anti-CD154 monoclonal antibodies (mAbs) showed potent immunosuppression but faced development challenges.
- An alternative approach targets the CD40 receptor, with ASKP1240 being a novel human anti-CD40 mAb.
Purpose of the Study:
- To evaluate the efficacy of ASKP1240 in preventing hepatic allograft rejection in nonhuman primates (NHPs).
- To test the hypothesis that CD40 blockade by ASKP1240 facilitates hepatic allograft acceptance.
- To assess the safety profile of ASKP1240 in NHPs undergoing liver transplantation.
Main Methods:
- Nonhuman primates received either a 2-week induction treatment or a 6-month maintenance monotherapy with ASKP1240.
- Hepatic allograft survival and function were monitored.
- Cellular and humoral alloimmune responses were assessed.
- Thromboembolic complications and other side effects were evaluated.
Main Results:
- A 2-week ASKP1240 induction treatment prolonged liver allograft survival but did not prevent chronic rejection.
- A 6-month ASKP1240 maintenance monotherapy effectively suppressed alloimmune responses and prevented hepatic allograft rejection.
- No serious adverse events, including thromboembolic complications, were observed in ASKP1240-treated NHPs.
Conclusions:
- CD40 blockade with ASKP1240 is a potential strategy for inducing tolerance in liver transplantation.
- Long-term ASKP1240 maintenance monotherapy demonstrates significant immunosuppressive effects and prevents chronic rejection.
- ASKP1240 represents a promising and safe immunosuppressant for clinical liver transplantation.
