ARK102:一种靶向TROP2、HER2和CD3的新型三特异性T细胞衔接器,用于治疗实体瘤

ARK102 is a novel trispecific T‑cell engager in a fragment format lacking an Fc domain, engineered using proprietary platform technology to simultaneously target HER2 and TROP2 while recruiting CD3 T cells for potent redirected cytotoxicity. HER2 and TROP2 are clinically validated tumor‑associated antigens that have demonstrated favorable outcomes across multiple therapeutic modalities. However, limited target expression in some tumors can restrict therapeutic efficacy. As HER2 and TROP2 are broadly co‑expressed across diverse malignancies, dual targeting of these antigens offers an innovative strategy to enhance tumor binding through increased avidity and to overcome challenges such as tumor heterogeneity, antigen loss, and resistance to existing therapies.Comprehensive in vitro analyses showed that ARK102 effectively binds both target antigens, activates T cells, and mediates T‑cell-dependent cytotoxicity in dual and single target‑expressing cancer cell lines at sub‑nanomolar concentrations. In vivo, ARK102 demonstrated robust, dose‑dependent antitumor activity in human PBMC‑reconstituted immunodeficient mice bearing HER2‑ and/or TROP2‑expressing tumor xenografts, without dose‑limiting toxicity at efficacious doses, and showed antitumor efficacy comparable to or greater than that of benchmark TROP2‑ADC and HER2‑ADC therapies.Together, these results highlight ARK102 as a potent and selective dual‑targeting T‑cell engager with the potential to expand treatment options for patients with solid tumors co‑expressing HER2 and TROP2. The compelling preclinical efficacy and favorable safety profile strongly support its further clinical evaluation.