Enhancing T Cell Activation: The Preclinical Profile of GLS-010 (AB122) Anti-PD-1 Antibody

Exhausted T cells, which are prevalent in the tumor microenvironment, express high levels of immune checkpoint proteins such as programmed death-1 (PD-1). The PD-1/PD-L1 pathway is known to facilitate tumor evasion by suppressing immune responses. GLS-010 (AB122) is a novel fully human anti-PD-1 monoclonal antibody that is currently in Phase 1 clinical trials and has been characterized preclinically for its potential in oncology.

GLS-010 (AB122) has been shown to have high affinity for human and cynomolgus monkey PD-1, with no cross-reactivity with rat or mouse PD-1. It specifically binds to PD-1 without interacting with other CD28 family members like ICOS, CD28, and CTLA-4. The antibody effectively inhibits the interaction of PD-1 with both PD-L1 and PD-L2, as demonstrated through flow cytometry and reporter gene assays.

Functional studies have revealed that GLS-010 (AB122) enhances the production of IFN-g and promotes the proliferation of CD4+ T cells in a dose-dependent manner. It also boosts antigen-specific T cell recall responses, as observed in assays using CMV-infected donors. In vivo, GLS-010 (AB122) has demonstrated significant anti-tumor efficacy in a mouse MC-38 tumor model involving mice transgenic for human PD-1.

Pharmacokinetic analysis in cynomolgus monkeys indicated that GLS-010 (AB122) exhibits dose-proportional profiles and dose-independent clearance rates after a single intravenous dose. The antibody's ability to potently enhance T cell activation, combined with its in vivo efficacy and pharmacokinetic profile, supports the ongoing clinical development of GLS-010 (AB122) as a therapeutic agent for cancer treatment.