A Boron Delivery Antibody (BDA) with Boronated Specific Residues: New Perspectives in Boron Neutron Capture Therapy from an In Silico Investigation

Boron Neutron Capture Therapy (BNCT) is a tumor cell-selective radiotherapy based on a nuclear reaction that occurs when the isotope boron-10 ((10)B) is radiated by low-energy thermal neutrons or epithermal neutrons, triggering a nuclear fission response and enabling a selective administration of irradiation to cells. Hence, we need to create novel delivery agents containing (10)B with high tumor selectivity, but also exhibiting low intrinsic toxicity, fast clearance from normal tissue and blood, and no pharmaceutical effects. In the past, boronated monoclonal antibodies have been proposed using large boron-containing molecules or dendrimers, but with no investigations in relation to maintaining antibody specificity and structural and functional features. This work aims at improving the potential of monoclonal antibodies applied to BNCT therapy, identifying in silico the best native residues suitable to be substituted with a boronated one, carefully evaluating the effect of boronation on the 3D structure of the monoclonal antibody and on its binding affinity. A boronated monoclonal antibody was thus generated for specific (10)B delivery. In this context, we have developed a case study of Boron Delivery Antibody Identification Pipeline, which has been tested on cetuximab. Cetuximab is an epidermal growth factor receptor (EGFR) inhibitor used in the treatment of metastatic colorectal cancer, metastatic non-small cell lung cancer, and head and neck cancer.