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Cetrelimab (JNJ 63723283; JNJ 3283) is a human IgG4κ mAb targeting PD-1. Cetrelimab binds PD-1 (Kd=1.72 nM, HEK293) to block the interaction of PD-1 with PD-L1 and PD-L2 (IC50s=111.7 ng/mL and 138.6 ng/mL, respectively). Cetrelimab stimulates peripheral T cells, increases IFN-γ, IL-2, TNF-α level and inhibits tumor growth in vivo[1]. | [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. |
| [References]
[1] DeAngelis N, et al. Discovery and pharmacological characterization of cetrelimab (JNJ-63723283), an anti-programmed cell death protein-1 (PD-1) antibody, in human cancer models. Cancer Chemother Pharmacol. 2022 Apr;89(4):515-527. DOI:10.1007/s00280-022-04415-5 |
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