IN30758，一种靶向整合素的抗体药物偶联物（ADC），在多种实体瘤中展现出强效治疗效果

Integrins represent a promising target for the development of antibody-drug conjugates (ADCs). The integrin alphaVbeta6 has already been leveraged in the creation of a clinical-stage ADC, which has demonstrated favorable efficacy and safety profiles in early assessments. The integrin family consists of 24 heterodimers formed by 18 alpha and 8 beta subunits. In this study, we present ADC IN30758, which comprises the integrin antibody A28 and a clinically validated linker payload, LD38. The binding affinities of both the unconjugated antibody and the ADC to the human integrin antigen are comparable. A28 exhibits strong antibody-antigen binding characteristics, facilitating effective association and dissociation. Both the unconjugated antibody and the ADC demonstrate significant internalization capabilities in cancer cells. Immunohistochemistry (IHC) staining assays indicate that A28 can bind to various solid tumors, including non-small cell lung cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), and ovarian cancer (OC). Various animal models, including cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) trials, were conducted to assess the tumor growth inhibition effects of IN30758, revealing that the ADC shows promising sensitivity across multiple solid tumors. Currently, the Investigational New Drug (IND) package, which includes preclinical efficacy, pharmacokinetics, and toxicity data, has been compiled, with the IND application expected to be submitted in December 2025.