Cetrelimab (JNJ 63723283; JNJ 3283) 是一种靶向PD-1的人源化 IgG4κ 单克隆抗体。Cetrelimab 结合PD-1的 Kd为 1.72 nM (HEK293 细胞)。由此，Cetrelimab 阻断PD-1与PD-L1和PD-L2的相互作用 (IC50分别为 111.7 ng/mL 和 138.6 ng/mL)。Cetrelimab 还刺激外周 T 细胞，增加细胞因子 (IFN-γ,IL-2,TNF-α) 水平，并抑制体内肿瘤生长。
| 生物活性 | Cetrelimab (JNJ 63723283; JNJ 3283) is a humanized IgG4κ mAb targetingPD-1. Cetrelimab bindsPD-1(Kd=1.72 nM, HEK293) to block the interaction ofPD-1withPD-L1andPD-L2(IC50s=111.7 ng/mL and 138.6 ng/mL, respectively). Cetrelimab stimulates peripheral T cells, increasesIFN-γ,IL-2,TNF-αlevel and inhibits tumor growth in vivo[1]. |
| IC50& Target | PD-1/PD-L1, PD-1/PD-L2, IFN-γ, IL-2, and TNF-α[1] |
体外研究
(In Vitro) | Cetrelimab (0.01-30 nM; 5 d) binds to endogenous PD-1 on activated CD4+and CD8+T cells with EC50s of 0.16-0.22 μg/mL and 0.17-0.22 μg/mL, respectively[1].
Cetrelimab (0.01-30 μg/mL; 24 h) reverse PD-1-mediated suppression of TCR signaling in Jurkat-PD-1 NFAT reporter cells with CHO-K1 expressing PD-L1[1].
Cetrelimab (0.001-100 nM; 6 d) increases IFN-γ, IL-2, and TNF-α with EC50s of 0.08 ng/mL, 0.07 ng/mL, and 0.02 ng/mL, respectively[1].
Cetrelimab binds to PD-1 in cynomolgus with a Kdvalue of 0.9 nM[1].
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体内研究
(In Vivo) | Cetrelimab (10 mg/kg; i.p.; single dose) has antitumor efficacy, and decreases tumor volume in PD-1 knock-in (hPD-1KI) mice with MC38 tumor[1].
Cetrelimab (10 mg/kg; i.p.; once every 5 days for 30 d) results significant increases in peripheral blood CD8+T cells in patient-derived xenograft (PDX) lung model in mice[1].
Cetrelimab (10-100 mg/kg; i.v.; once weekly for 5 weeks) has well tolerance in cynomolgus model[1].
Cetrelimab (0.1-10 mg/kg; i.v.; single dose, monitored for 57 d) shows an nonlinear pharmacokinetics (PK) in cynomolgus, possibly attributable to target-mediated drug deposition (TMDD)[1].
| Animal Model: | hPD-1KI model with mouse PD-1 ECD replaced by the human PD-1 ECD[1] | | Dosage: | 10 mg/kg | | Administration: | Intraperitoneal injection; single dose at day 7 after tumor implantation | | Result: | hPD-1KI mice develop normally and have no immune abnormalities.
Significantly lowered tumor volume at Day 21. |
| Animal Model: | Patient-derived xenograft (PDX) LG1306 lung model in mice[1] | | Dosage: | 10 mg/kg | | Administration: | Intraperitoneal injection; every 5 days for 6 cycles | | Result: | Significantly reduced patient-derived tumor volume by 32%. |
| Animal Model: | Good Laboratory Practice (GLP) toxicity study in cynomolgus[1] | | Dosage: | 0, 10, 30, or 100 mg/kg | | Administration: | Intravenous injection; once weekly for 5 weeks | | Result: | Showed well tolerance in cynomolgus. |
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| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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