(565f) Engineered Anti-CD276 Mab to Deliver Payload for Cancer Treatment

Targeted therapies or combined therapies are effective to treat aggressive, heterologous and recurrent cancers as compared to standard chemotherapies. This study aimed to develop an engineered anti-CD276 monoclonal antibody (mAb)-drug conjugate to treat triple-negative breast cancers (TNBCs). Specifically, CD276 surface receptor was identified as an ideal target of over 60% TNBC patients. An innovative murine anti-human mAb was developed to target the N-glycosylated extracellular domain (Leu29-Pro245) of CD276 receptor, further engineered to construct a new chimeric mAb, and conjugated with payload mertansine to construct antibody-drug conjugate (ADC). The flow cytometry analysis, confocal microscopy imaging, and In Vivo Imaging System demonstrated the capability to specifically target CD276⁺ TNBC of our mAb. The IC₅₀ assay showed high anti-TNBC cytotoxicity of constructed ADC in multiple cell lines. Furthermore, in vivo anti-tumor evaluations using immunocompetent mouse models and patient-derived xenograft (PDX) models demonstrated high tumor treatment efficacy of the anti-CD276 ADC which integrates the advantages of potency of mertansine and tumoral immunity of CD276 mAb. This study suggested that our anti-CD276 mAb-based ADC could provide a promising targeted therapy for TNBC patients in future.