Pre‐clinical results in pig‐to‐non‐human primate islet xenotransplantation using anti‐CD40 antibody (2C10R4)‐based immunosuppression

Abstract

These results showed that anti-CD40 mAb combined with tacrolimus was effective in prolonging porcine islet graft survival, but anti-CD40 mAb was not as effective as anti-CD154 mAb in terms of preventing early islet loss.

PERVading strategies and infectious risk for clinical xenotransplantation

“…The recent improvements in efficacy and survival of pre‐clinical renal, islet, and cardiac xenotransplantation have reinvigorated interest in clinical xenotransplantation. This renewed interest makes it essential for clinicians, regulators, and the general public and potential patients to have a clear understanding of the risk represented by porcine endogenous retrovirus (PERV).…”

Xenotransplantation literature update, January/February 2018

“…However, in the case of the study using anti-CD40 mAb, unfortunately some transplants underwent graft rejection and loss of function as quickly as one week following transplantation. 15 This was rather unfortunate as it is at odds with other groups that have reported successful long-term survival of allo islets 16 and heterotopic TG pig hearts in baboons using the same anti-CD40 mAb. 17 It may well be that there is in fact a role for the use of the TG pig islets as they provide protection in overcoming the initial instant blood-mediated inflammatory reaction (IBMIR) response to the porcine islets that WT pig islets alone cannot, 7 IBMIR).…”

The 2017 IXA Presidential Lecture: Recent developments in xenotransplantation

“…Belatacept is approved for clinical solid organ transplantation, and anti‐CD40 is the subject of phase 2 clinical trials in renal transplantation . “High dose” anti‐CD40 was a key component of the protocol used to achieve long‐term cardiac xenograft survival, although some evidence suggests that anti‐CD154 may be more effective than anti‐CD40, at least in the preclinical islet model . However, anti‐CD154 in its current form cannot be used clinically, as clinical trials were halted due to the unexpected development of thromboembolic events in some patients.…”