CD40 (cluster of differentiation 40) is a costimulatory protein found on antigen-presenting cells (APC). Its receptor belongs to the TNF-receptor superfamily and is important for immune and inflammatory responses, including T cell-dependent immunoglobulin class switching, memory B cell development, and so on. CD154, located on TH cells, can bind to CD40, then activate APC and induce downstream effects. However, overactive immune responses may lead to rejection during organ transplantation, resulting in treatment failure. Following existing research, the blockade of CD40-CD154 signaling can induce potent immunosuppression and tolerance in experimental organ transplantations in rodents. Therefore, the development of anti-CD40/CD154 agents has become a strategy for preventing organ transplant rejection.

Bleselumab (ASKP 1240) is an anti-CD40 monoclonal antibody (mAb).

From: Yoon CH, et al. Prog Retin Eye Res. 2021 Jan;80:100876.

Bleselumab binds to human CD40 with high affinity (Kd = 0.24 nM). It inhibits immune responses by blocking the interaction of CD40 with its ligand CD40L (CD40 ligand). For example, in vitro, Bleselumab (0-1 μg/mL, 48 h) inhibits PBMC proliferation induced by shCD154 in human, cynomolgus monkey, and rabbit blood samples in a dose-dependent manner.

Besides, in vivo, Bleselumab (0.1-10 mg/kg, i.v.) inhibits anti-TTx IgG and anti-TTx IgM productions in a concentration-dependent manner, then inhibit delayed-type hypersensitivity (DTH) reaction in cynomolgus monkeys. Furthermore, Bleselumab (2 mg/kg, i.v.) prolongs renal allograft survival in Cynomolgus monkeys. In addition, Bleselumab (2 or 5 mg/kg, i.v.) together with Tacrolimus shows a longer median survival time (MST) than monotherapy. Excitingly, it has been tried in clinical settings.

In conclusion, Bleselumab is a potent anti-CD40 mAb and has been proven that effectively prolongs renal allograft survival in cynomolgus monkeys.


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