Advancements in antibody-drug conjugates (ADCs) have introduced promising therapeutic strategies for challenging malignancies such as Triple-Negative Breast Cancer (TNBC). This research introduces three novel CD276-based DualADC platforms aimed at the treatment of Triple-Negative Breast Cancer (TNBC). These DualADCs synergistically combine a chemotherapeutic agent with an immune boosting reagent, targeting cancer cells directly while simultaneously enhancing immune system responses. We selected DM1, MMAF, and DXd as the chemotherapeutic agents and paired each with a TLR 7/8 agonist to amplify immune activation. The integrity and successful conjugation of these DualADCs were verified through SDS-PAGE, HPLC, and LC-MS techniques. Efficacy trials were conducted both in vitro using TNBC cell lines and in vivo employing mouse models with TNBC tumors, including models with human tumor xenografts and patient-derived xenografts (PDX). All results demonstrate that all DualADCs are effective in inhibiting or eliminating TNBC cells and enhancing immune functions. Incorporating the CD276 monoclonal antibody, which acts as an immune checkpoint inhibitor, these DualADCs show potential for robust and durable therapeutic outcomes against TNBC. This integrated approach of combining chemotherapeutic and immunotherapeutic strategies within a single treatment presents a promising pathway for addressing the challenges posed by aggressive TNBC.
