CBT-502 (TQB2450) is a distinctive humanized IgG1 antibody that targets the
programmed cell death-ligand 1 (PD-L1), with substantial sequence divergence in complementarity-determining regions (CDRs) compared to existing anti-PD-L1 antibodies such as
atezolizumab,
durvalumab, and
avelumab. PD-L1's expression is notably high in various human
cancer cells and plays a critical role in inhibiting cytotoxic T cells by binding to
PD-1 and
CD80. The therapeutic blockade of PD-L1 has been shown to reduce tumor growth when immune cells are present.
In vitro studies have confirmed CBT-502's high binding affinity to human PD-L1, with a dissociation constant (KD) of 0.25 nM as measured by surface plasmon resonance (SPR). The antibody effectively prevents the interaction between human PD-1 and PD-L1, with an IC50 of 47.97 pM, and also inhibits PD-L1's binding to CD80 with an IC50 of 1.09 nM. CBT-502 has been shown to robustly activate T cells, as evidenced by IFN-gamma production in a mixed lymphocyte reaction assay.
Pharmacokinetic studies in cynomologus monkeys have demonstrated a linear dose-dependent relationship for CBT-502. The antibody has shown no affinity for
Fc receptors, including FcgRIa, FcgRIIa-167His/Arg,
FcgRIIIa-176Phe/Val,
FcRn, and
C1Q, as determined by SPR. In toxicology screens, no adverse effects were observed at a no-observed-adverse-effect-level (NOAEL) of 200 mg/kg.
In vivo antitumor activity of CBT-502 was assessed in two mouse models: A375 (
melanoma) and MC-38/H-11 (
colon cancer). In the MC-38/H-11 model, CBT-502 showed comparable tumor growth inhibition (TGI) rates to atezolizumab at a dose of 15 mg/kg. In the A375 model, CBT-502 exhibited potent dose-dependent antitumor activity, with TGI percentages of 53.5% at 10 mg/kg administered three times weekly, compared to 59.4% for atezolizumab at the same dosage. Notably, CBT-502 did not lead to significant body weight loss, unlike atezolizumab which caused a slight reduction at 10 mg/kg three times weekly.
The preclinical pharmacodynamics and toxicology studies indicate that CBT-502 has pharmacological activity and is well tolerated at effective doses, offering a wide safety margin. The in vivo efficacy and safety data in the A375 model were favorable when compared to atezolizumab, and the MC38 model confirmed the activity of CBT-502. Based on these promising nonclinical data,
CBT Pharmaceuticals and their China partner CTTQ are planning to develop and evaluate CBT-502 in
multiple solid tumors.
The research was presented by Zhao Wei, Ling Yang, and colleagues at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in 2017.
How to Use Synapse Database to Search and Analyze Translational Medicine Data?
The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

Click on the image below to go directly to the Translational Medicine search interface.
