Demonstrates enhanced tumor control in solid tumors using novel CD3 binders that decrease harmful cytokine release, suggesting improved therapy safety.
Key Points
The research aims to improve T cell engagers (TCEs) by developing non-polyreactive CD3 binders for enhanced anti-tumor effects with fewer side effects.
Employed a nanoparticle-based immunization platform in the OmniRat transgenic model.
Identified and produced recombinant monoclonal antibodies from immunization hits.
Assessed TCEs for non-specific activation and cytotoxicity in vitro and in vivo.
Characterized novel CD3 binders focusing on their interaction with human and NHP T cells.
Identified 12 sequence families of CD3 binders, with 5 showing no detectable polyreactivity.
TCEs with novel CD3 binders demonstrated effective tumor-cell killing with less cytokine release compared to SP34-based TCEs.
SCRI-6 clone exhibited significantly lower non-specific T cell activation than SP34 TCEs when used with costimulation.
TCEs incorporating SCRI-6 showed comparable potency to existing therapies in solid and liquid tumor models.