This study presents the development of a bispecific molecule combining an anti-PD-1 antibody with a multimeric GITR ligand (GITR-L), designed to induce PD-1-dependent and FcγR-independent GITR clustering. This mechanism enhances activation, proliferation, and memory differentiation of antigen-specific GITR⁺PD-1⁺ T cells. The bispecific agonist demonstrated dose-dependent tumor growth inhibition in various mouse tumor models, including syngeneic, genetically engineered, and humanized xenograft models. The study highlights the potential of this bispecific approach to overcome limitations of previous GITR agonists by optimizing receptor clustering for effective T cell activation.
The anti-PD-1–GITR-L bispecific agonist effectively induces T cell activation and tumor growth inhibition through optimized GITR clustering, offering a promising strategy for cancer immunotherapy.
Human PD-1 and GITR Knockin mouse models, developed by genOway, were utilized to evaluate the efficacy and mechanism of the bispecific agonist in an immunocompetent setting.
Cancer immunotherapy, T cell activation, Bispecific agonist, GITR clustering, PD-1 pathway
Humanized Knockin models, PD-1 and GITR gene targeting, Immunocompetent mouse models
From model design to experimental results
Tailor-made solutions adapted to scientific questions
Comprehensive dataset package
Generated with biopharma partners and in-house
Scientific follow-up and advice along the project
Collaborative approach for problem solving and development of innovative models
Breeding facilities in US and Europe
Certified health status from professional breeders
