Abstract 5637: A novel EGFR and B7H3 dual-targeted antibody-drug conjugate (ADC) for the treatment of solid tumors

Abstract Background: EGFR (also known as HER1) is an epidermal growth factor receptor involved in tumor progression, and its overexpression in approximately 70% of colorectal cancer (CRC), 60% of lung cancers, and over 90% of head and neck squamous cell carcinoma (HNSCC). B7H3 belongs to the B7 immunoregulatory family. B7H3 is overexpressed on a wide range of solid tumors such as lung cancers, gastrointestinal cancers and gynecological cancers, but its expression is absent or low in normal tissues. Therefore, dual targeting of both EGFR and B7H3 can achieve better therapeutical efficacy. EGFR/B7H3-ADCs are novel bispecific Antibody-drug Conjugates (ADCs), composed of fully human anti-EGFR/B7H3 bispecific antibodies (BsAbs) conjugated to TOP1i payload via cleavable linker. Methods: the fully human monoclonal antibodies were derived from transgenic mouse model NeoMab mice. Flow cytometry was performed to examine binding of ADCs to tumor cells. In addition, we used pHrodo conjugated to ADCs to detect internalization activity in tumor cells. CTG (CellTiter-Glo®) assay was employed to measure cell viability. In immunodeficient mice, xenograft model was generated to assess the tumor growth inhibition of ADCs. Results: EGFR/B7H3-ADCs showed stronger binding to tumor cells than EGFR-ADC and B7H3-ADC. Besides, EGFR/B7H3-ADCs displayed superior internalization activity. More importantly, our EGFR/B7H3-ADCs suppressed tumor growth more effectively than EGFR-ADC and B7H3-ADC in CDX mouse model. Conclusion: our EGFR/B7H3-ADCs show potential therapeutic promise in patients with EGFR or B7H3 positive tumors. This study provides crucial rationale for supporting the further development of our novel dual-targeted Antibody-drug Conjugates (ADCs). Citation Format: Mingkun Zhang, Xuguo Zhu, Jun Wang, Jing Zhao. A novel EGFR and B7H3 dual-targeted antibody-drug conjugate (ADC) for the treatment of solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5637.