A fully human monoclonal antibody targeting PD-L1 with potent anti-tumor activity

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• The programmed cell death ligand-1 (PD-L1) and its receptor PD-1 pathway are frequently overactivated in various tumors.
• Inhibiting the PD-L1/PD-1 interaction is a key strategy to restore anti-tumor T cell immunity.

Purpose of the Study:

• To identify and characterize a novel fully human anti-PD-L1 monoclonal antibody (mAb) for cancer immunotherapy.
• To evaluate the binding affinity, specificity, and functional activity of the anti-PD-L1 mAb B60-55.

Main Methods:

• Yeast surface display was employed to identify the fully human anti-PD-L1 mAb B60-55.
• In vitro and in vivo studies assessed mAb B60-55's affinity, specificity, T cell-enhancing activity, and anti-tumor efficacy.

Main Results:

• mAb B60-55 demonstrated high affinity (Kd = 0.2 nM) for human and cynomolgus PD-L1, with no cross-reactivity to murine PD-L1.
• The antibody functions antagonistically, blocking PD-L1 binding to PD-1 and B7.1 (CD80), and enhances T cell responses and cytokine production.
• In vivo studies showed potent anti-tumor activity against carcinoma xenografts, with a favorable half-life in non-human primates.

Conclusions:

• mAb B60-55 exhibits significant potential as a therapeutic agent for cancer treatment.
• Further clinical development of mAb B60-55 is warranted based on its preclinical profile.