SCRI-6

SCRI-6 is a novel, high-affinity, non-polyreactive monoclonal antibody clone that binds specifically to the CD3δε subunit of the T-cell receptor complex. Identified through a nanoparticle-based immunization platform in transgenic rats, SCRI-6 was developed by researchers at the Seattle Children's Research Institute. Unlike traditional CD3 binders such as SP34, SCRI-6 exhibits no detectable polyreactivity and is cross-reactive with non-human primate CD3. When incorporated into bispecific T-cell engagers (TCEs) targeting antigens like PD-L1, DLL3, or CD19, SCRI-6 facilitates potent tumor cell killing with significantly reduced secretion of inflammatory cytokines (IFNγ, IL-6, TNFα) and minimal non-specific T-cell activation. This improved therapeutic index allows for the safe pairing of SCRI-6-based TCEs with costimulatory domains (e.g., CD28 or 4-1BB) to enhance anti-tumor efficacy and T-cell persistence in solid and liquid tumors.