Modification of nitric oxide donors onto a monoclonal antibody boosts accumulation in solid tumors

Although monoclonal antibodies (mAbs) have revolutionized cancer treatment, their accumulation in solid tumors is limited and requires improvement to enhance therapeutic efficacy. Here we developed a strategy to modify mAb with a donor of nitric oxide (NO) because NO functions to vasodilate as well as to enhance the permeability of vascular endothelium, which will contribute to enhancing the tumor accumulation of mAb. We selected S-nitrosothiol as a NO donor and established the procedure to modify S-nitrosothiol group on mAb under ambient conditions. The modified mAb (Ab-SNO) thus obtained released NO in a preferable speed and maintained its original properties such as binding affinity to a target antigen and efficacy to induce antibody-dependent cellular cytotoxicity. We demonstrated that Ab-SNO enhanced the tumor accumulation of co-administered proteins such as antibody and serum albumin.