Preclinical pharmacology characterization of HX009, a novel PD1 x CD47 Bi-specific antibody.

ABSTRACT: Certain immune-checkpoint inhibitors have a narrow therapeutic window (TW) as cancer therapeutics, and engineered dual-/multi-targeting agents could potentially widen the TW to bring true clinical benefits. We report a new rationally-designed bispecific-antibody (BsAb), HX009, simultaneously targeting PD1 and CD47 to improve both the efficacy and safety over the respective single-targeting agents by grafting the extracellular domain of SIRPα onto the parental anti-PD1-monoclonal antibody, HX008. This resulted in an IgG4-based "2 × 2" symmetric structure but with an intentionally-reduced CD47-binding affinity, suggesting a novel candidate cancer immunotherapy. Specifically, HX009 has binding affinity constant of 8.951 × 10^-9 M for human PD1 and 2.557 × 10^-8 M for human

SUBMITTER: Ke H 

PROVIDER: S-EPMC11567960 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature