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Updated: Dec 20, 2025
Testing Cancer Immunotherapeutics in a Humanized Mouse Model Bearing Human Tumors
Published on: December 16, 2022
CS1003, a novel human and mouse cross-reactive PD-1 monoclonal antibody for cancer therapy
Fu Li1, Jingrong Li1, Ke Yin1
1CStone Pharmaceuticals (Suzhou) Co., Ltd, Shanghai, 201203, China.
Abstract:
The programmed cell death protein 1 (PD-1) is an immune-checkpoint that negatively regulates the immune system and a key mechanism that tumors utilize to escape from immune surveillance. PD-1 antibodies can block the interaction of PD-1 with its ligands (PD-L1 and PD-L2), restore T cells activation, and elicit antitumor activity. In this paper, we reported a novel PD-1 monoclonal antibody (mAb) CS1003, which is a humanized IgG4 PD-1 mAb generated by conventional hybridoma technology, and currently being developed in multiple clinical trials as monotherapy or in combination with other anticancer agents. We showed that CS1003 bound to recombinant human, cynomolgus monkey, and mouse PD-1 with EC50 values of 0.1757, 0.2459, and 0.3664 nM, respectively. CS1003 blocked PD-1 interaction with its ligands, dose-dependently enhanced T cell proliferation and secretion of cytokines (IL-2 and IFN-γ) to the levels comparable to the reference antibody pembrolizumab. Intraperitoneal administration of CS1003 (0.1, 0.5, 2.5 mg/kg, once every 3 days) dose-dependently suppressed the growth of MC38-hPD-L1 colon cancer in hPD-1 knock-in mice. Pharmacokinetics (PK) study revealed a linear PK profile within the dose range of 2-18 mg/kg following single intravenous administration in cynomolgus monkey. These data provide a comprehensive preclinical characterization of CS1003 that supports its clinical development for cancer immunotherapy.
Insights
A novel humanized monoclonal antibody, CS1003, effectively blocks programmed cell death protein 1 (PD-1) immune checkpoints. Preclinical studies demonstrate CS1003
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Programmed cell death protein 1 (PD-1) is an immune checkpoint protein that tumors exploit to evade immune surveillance.
- PD-1 antibodies can restore T-cell activation by blocking PD-1 interactions with its ligands, leading to antitumor activity.
Purpose of the Study:
- To characterize a novel humanized IgG4 PD-1 monoclonal antibody, CS1003, for cancer immunotherapy.
- To evaluate the preclinical efficacy and pharmacokinetic profile of CS1003.
Main Methods:
- CS1003 binding affinity to human, cynomolgus monkey, and mouse PD-1 was determined.
- In vitro assays assessed CS1003's ability to block PD-1/ligand interaction and enhance T-cell proliferation and cytokine secretion.
- In vivo efficacy was evaluated in MC38-hPD-L1 colon cancer models in hPD-1 knock-in mice, and pharmacokinetics were studied in cynomolgus monkeys.
Main Results:
- CS1003 demonstrated high binding affinity to PD-1 across species and effectively blocked PD-1/ligand interactions.
- CS1003 significantly enhanced T-cell proliferation and cytokine production in vitro, comparable to pembrolizumab.
- CS1003 dose-dependently suppressed tumor growth in vivo and exhibited linear pharmacokinetics in non-human primates.
Conclusions:
- CS1003 is a potent PD-1 inhibitor with comprehensive preclinical characterization.
- These findings support the ongoing clinical development of CS1003 for cancer immunotherapy.
