Abstract 1279: Preclinical syngeneic model and xenograft model for evaluating CD3/HER2 bispecific antibody therapy

Abstract Abnormal expression of HER2 in normal cells and tissues makes them susceptible to carcinogenesis, leading to tumor formation. HER2 gene amplification or protein overexpression has been found in various human tumors, including breast cancer, gastric cancer, and ovarian cancer. The approval of multiple anti-HER2 drugs has greatly improved the prognosis for patients with HER2-positive solid tumors. However, in clinical practice, some HER2-positive patients have developed resistance, possibly due to an immunosuppressive tumor microenvironment (TME). The CD3/HER2 bispecific antibody (BsAb) is considered a strategy to overcome this immunosuppressive TME by redirecting T cells to HER2-expressing tumor cells, thereby killing HER2-positive tumor cells. Biocytogen developed a BsAb Ab1 that targets human CD3 and human HER2, and evaluated its efficacy and mechanism of action in preclinical studies. In vitro cytotoxicity assays showed that CD3/HER2 BsAb Ab1 significantly induced T cell activation and exhibited effective killing effects against B-hHER2 MC38 plus cell line expressing human HER2. In a syngeneic transplantation model using B-hCD3E/hHER2 mice inoculated with the B-hHER2 MC38 plus cell line, BsAb Ab1 effectively inhibited tumor growth. Additionally, CD3/HER2 BsAb also significantly inhibited the growth of human tumor cells NCI-N87 in a PBMC reconstitution model using B-NDG mice. These results indicate that both models are suitable for the preclinical evaluation of the CD3/HER2 BsAb. Citation Format: Fengqian Chen, Chong Li, Qinjun Wang, Qiang Liu, Baihong Liu, Jiansu Zhang, Xiaofei Zhou. Preclinical syngeneic model and xenograft model for evaluating CD3/HER2 bispecific antibody therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1279.