(497d) CD276 mAb-MMAF to Treat Non-Small Cell Lung Cancer

Non-small-cell lung cancer (NSCLC) counts for a significant portion of lung cancers and is associated with high mortality rates. Traditional chemotherapy, radiotherapy and biological therapies have shown limited clinical efficacy and severe side effects. Therefore, the development of novel, targeted therapeutics is crucial to improve the life quality of NSCLC patient. In this study, we developed a novel anti-CD276-targeted antibody-drug conjugate (ADC), i.e. CD276-MMAF, for NSCLC treatment. First, we developed an anti-CD276 monoclonal antibody (mAb) using hybridoma technology, which can specifically bind to the surface CD276 on both human and mouse NSCLC cells as confirmed in flow cytometry analysis. Second, a fed-batch production using hybridoma cell line and protein A column-based purification process was developed to generate large-scale mAb. Third, CD276 mAb was conjugated with the cytotoxic monomethyl auristatin F (MMAF) via a cleavable dipeptide-based linker to construct antibody-drug conjugate (ADC). Cytotoxicity assay showed that ADC can effectively killed NSCLC cells such as A549, H460 and LLC. The in vivo studies in NSCLC xenograft mouse models revealed high anti-cancer efficacy, tumoral immunity, cancer specificity, and minimal toxicity of our CD276 ADC. In conclusion, our study developed and evaluated a novel CD276-targeted ADC as a promising therapeutic option for patients with NSCLC. Further translational investigations will be performed to determine the toxicology, optimal dose, and treatment strategy.