T-Cell Engagers Based Bioassay for Evaluation of PD-1/PD-L1 Inhibitors Activity

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) therapies represent a significant advancement in cancer treatment.
• Numerous anti-PD-1 and anti-PD-L1 antibodies are in development, necessitating robust methods for activity characterization.
• Accurate bioassays are essential for determining the biological activity of these immunotherapeutic antibodies.

Purpose of the Study:

• To develop and characterize a novel cell-based bioassay for analyzing the activity of anti-PD-1 and anti-PD-L1 antibodies.
• To compare different effector cell activation strategies for their suitability in the bioassay.
• To demonstrate the bioassay's applicability in the development and characterization of therapeutic agents.

Main Methods:

• Development of a two-cell-line reporter system.
• Evaluation of effector cell activation using superantigens, soluble anti-CD3, transmembrane anti-CD3, chimeric antigenic receptors (CARs), and bispecific T-cell engager antibodies.
• Characterization of the developed bioassay's performance.

Main Results:

• Bispecific T-cell engager antibodies demonstrated advantages for effector cell activation within the reporter system.
• The developed cell-based bioassay was successfully characterized.
• The bioassay proved applicable for analyzing the activity of anti-PD-1 and anti-PD-L1 antibodies.

Conclusions:

• A novel and effective cell-based bioassay for PD-1/PD-L1 antibody activity analysis has been established.
• The bioassay, particularly with bispecific T-cell engagers, offers a valuable tool for immunotherapy research.
• This assay can support the development and characterization of new cancer therapeutic agents.