Camrelizumab (SHR-1210), a humanized anti-PD-1 IgG4 mAb, exhibits superior anti-tumor activity and a favorable safety profile in preclinical studies

doi:10.5246/jcps.2021.05.031

Abstract

Abstract:

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.

Key words: Camrelizumab, PD-1, Binding epitope, Efficacy, Safety, VEGFR2

Supporting:

Xing Sun, Changyong Yang, Kan Lin, Caihong Zhou, Chen Liao, Limin Zhang, Xinsheng Jin, Langyong Mao, Hua Ying, Weikang Tao, Lianshan Zhang. Camrelizumab (SHR-1210), a humanized anti-PD-1 IgG4 mAb, exhibits superior anti-tumor activity and a favorable safety profile in preclinical studies[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(5): 393-408.

Figures/Tables 17

Table 1. The binding affinity of camrelizumab with PD-1 antigen from different species.

Table 2. The binding affinity of camrelizumab with human Fc receptors.

Table 3. Anti-tumor effect of camrelizumab in MC38 model in humanized PD-1 transgenic mice.

Table 4. Anti-tumor effect of camrelizumab in B16F10 model in humanized PD-1 transgenic mice.

Table 5. PK parameters of camrelizumab in cynomolgus monkey after a single intravenous infusion at 1, 3 and 10 mg/kg (n = 6, half/sex). Data were presented as mean ± SD.

Table 6. The binding affinity of different anti-PD-1 antibodies to human VEGFR2.

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