卡瑞利珠单抗是一种人源化的抗PD-1单克隆抗体.在体外与人和食蟹猴PD-1蛋白具有纳摩尔级别的高亲和力,但不结合鼠源PD-1蛋白.它在体外有效阻断PD-1/PD-L1信号通路的同时还可以激活T细胞.卡瑞利珠单抗与PD-1独特的结合表位同PD-1和PD-L1结合表位有部分的重叠,证明了卡瑞利珠单抗对PD-1/PD-L1具有很强的结合阻断活性.在PD-1转基因小鼠皮下移植瘤模型中,卡瑞利珠单抗可以显著抑制MC-38和B16F10两种细胞在小鼠体内的生长,抑瘤作用优于已上市的其它PD-1单抗.此外,卡瑞利珠单抗在食蟹猴中表现出良好的药代动力学和安全性特征.并且,我们发现了卡瑞利珠单抗具有很弱的VEGFR2结合活性,但即使在很高的剂量下也不会激活VEGFR2信号通路.综上所述,我们证明了卡瑞利珠单抗是优秀的肿瘤治疗药物,现有数据也支持其在临床实践中进一步探索其有效性和安全性.“,”Camrelizumab is a humanized monoclonal antibody (mAb) against human PD-1.It demonstrated a single digit nanomolar binding affinity to human and cynomolgus monkey PD-1,but no cross-reactivity to murine PD-1.It exhibited potent PD-1/PD-L1 blocking activity as well as the T cell activation in vitro.The distinct binding sites of cameralizumab were perfectly overlapped with the PD-L1 binding sites,which supported its excellent ability in blocking PD-1/PD-L1 interaction.It also significantly inhibited the growth of murine MC-38 and B16F10 cell in humanized PD-1 transgenic mice with a superior inhibitory effect compared with the other marketed anti-PD-1 antibodies.Furthermore,camrelizumab also displayed a favorable pharmacokinetic (PK) and safety profile in cynomolgus monkeys.Besides,we showed that camrelizumab only bound to VEGFR2 with a very low affinity and did not activate VEGF pathways even at very high doses.Collectively,we provided evidence that cameralizumab was an ideal therapeutic candidate for cancer treatment,encouraging further evaluation of its efficacy/safety in the clinical setting.