(174p) An Innovative Antibody-Drug Conjugate to Treat Non-Small Cell Lung Cancers

Non-small cell lung cancers (NSCLCs) represent a substantial population of lung cancers with high mortality rates. Traditional treatments such as chemotherapy, radiotherapy, and biological therapies have limited clinical benefits but significant side effects on patinets. Thus, the development of novel, targeted therapeutics is vital for enhancing the quality of life for NSCLC patients. In this study, we introduce a novel humanized anti-CD276 monoclonal antibody (mAb) and dual payloads conjugate (DualADC) for NSCLC treatment. First, we developed a stable Chinese Hamster Ovarian (CHO) cell line to express our humanized CD276 mAb and established a scalable biomanufacturing procedure, including a fed-batch production in stirred-tank bioreactor and liquid chromatography purification with protein A column. Our CD276 mAb demonstrated high binding efficiency and cancer specificity to various NSCLC subtypes in flow cytometry analysis. Then, we conjugated the humanized CD276 mAb with cytotoxic payload MMAF/DM1 and an immune boosting TLR agonist using our recently developed conjugation platform. The cytotoxicity assay showed that our CD276-targeting DualADC effectively killed multiple NSCLC cell lines, including H358, A549, H460 and LLC. Furthermore, the anti-cancer efficacy studies in multiple mouse models demonstrated that our ADC has high NSCLC treatment effectiveness with synergistic mechanisms, cancer specificity, and minimal toxicity. In summary, we have successfully designed and assessed a new CD276-targeted ADC for NSCLC treatment. Future research will aim to optimize the treatment strategy and fully evaluate the toxicology.