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 ona nuclear reaction that occurs when the isotope boron-10 (10B) is radiated by low-energy thermalneutrons or epithermal neutrons, triggering a nuclear fission response and enabling a selectiveadministration of irradiation to cells. Hence, we need to create novel delivery agents containing10B with high tumor selectivity, but also exhibiting low intrinsic toxicity, fast clearance from normaltissue and blood, and no pharmaceutical effects. In the past, boronated monoclonal antibodies havebeen proposed using large boron-containing molecules or dendrimers, but with no investigationsin relation to maintaining antibody specificity and structural and functional features. This workaims at improving the potential of monoclonal antibodies applied to BNCT therapy, identifying insilico the best native residues suitable to be substituted with a boronated one, carefully evaluatingthe 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 10B delivery. In this context, wehave developed a case study of Boron Delivery Antibody Identification Pipeline, which has beentested on cetuximab. Cetuximab is an epidermal growth factor receptor (EGFR) inhibitor used inthe treatment of metastatic colorectal cancer, metastatic non-small cell lung cancer, and head andneck cancer.