Abstract 6081: Bispecific antibody drug conjugates (bsADCs) targeting DLL3 and B7-H3 demonstrated potent anti-tumor activity in preclinical models of small cell lung cancer (SCLC)

作者：Kaiqing Zhang, Liu Yang, Peiran Li, Yu Bin Qi, Jushi Gai, Luheng Du, Gao An, Chengzhang Shang, Yanan Guo, Yi Yang, Frank An · 发表于：Cancer Research · 年份：2025 · DOI：10.1158/1538-7445.am2025-6081 · 被引用次数：3 · 研究领域：Lung Cancer Research Studies、Monoclonal and Polyclonal Antibodies Research、HER2/EGFR in Cancer Research

Abstract Lung cancer is the most common type of cancers and the leading cause of cancer-related mortality worldwide, with 2.5 million new cases and 1.8 million deaths in 2022. Small-cell lung cancer (SCLC) accounts for ∼15% of all lung tumors, representing the most aggressive high-grade neuroendocrine carcinoma with a five-year survival rate of less than 4%. The majority of patients are diagnosed with extensive stage SCLC (ES-SCLC) with brain metastases in ∼80% of cases, yielding a grim 5-year survival rate of under 2%. Many patients experience relapse following front-line therapies, and current second-line treatment options remain limited. Delta-like ligand 3 (DLL3) is highly expressed in SCLC, neuroendocrine tumors, and glioblastoma with minimally or no expression in normal tissues, making it an attractive target for SCLC. B7-H3, an immunoregulatory protein, is overexpressed in several tumor types, including SCLC. Both DLL3 and B7-H3 are validated targets for SCLC. Tarlatamab, a T cell engager targeting DLL3, was recently approved for SCLC. ADCs targeting DLL3 have shown robust anti-tumor activities in clinical trials. Similarly, anti-B7-H3 ADCs have also shown promising clinical potential. We constructed a series of bispecific ADC (bsADC) that target both DLL3 and B7-H3 (DLL3xB7H3) simultaneously for SCLC and other tumors expressing these markers. We hypothesized that dual targeting could enhance selectivity and potency, address tumor heterogeneity in tumoral DLL3 and B7-H...