Comprehensive characterization of DT-7012, a highly differentiated anti-CCR8 depleting antibody

Background: CCR8 has recently emerged as a promising target in the treatment of solid tumors. DT-7012 is a novel humanized anti-CCR8 IgG1 monoclonal antibody engineered for optimized binding and enhanced effector functions to preferentially deplete tumor-resident Tregs while maintaining peripheral immune integrity. Objectives: To complete the preclinical characterization of DT-7012, focusing on its binding properties, effector-function potencies, and selectivity compared with clinical-stage CCR8-targeting antibodies. Methods: A comprehensive series of in vitro assays were conducted to assess DT-7012's binding properties and functional activities. Data were compared against leading clinical-stage anti-CCR8 competitors to elucidate potential clinical advantages. Assays were conducted under tumor-microenvironment-mimicking conditions to evaluate functional robustness. Results: DT-7012 displayed a unique binding profile, conferring high-affinity interaction and superior FcgammaR engagement. In cell-based assays, DT-7012 induced potent selective killing activities, including under tumor-microenvironment-mimicking conditions. Collectively, these findings support DT-7012 as a potential best-in-class CCR8-depleting candidate. Conclusions: With distinct binding and effector characteristics, DT-7012 emerges as a promising therapeutic for selective modulation of the tumor microenvironment. These results provide the preclinical rationale for clinical evaluation in patients with advanced solid tumors. Keywords: DT-7012, CCR8, Treg depletion, ADCC, ADCP, tumor microenvironment, immuno-oncology.