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Antibody-mediated delivery of therapeutics has been primarily limited to agents containing amine, alcohol or thiol functional groups. Now, an approach has been developed to create stable and bio-reversible prodrugs that mask ortho-quinones. Drug release requires both protease activation followed by acid-assisted elimination. One of the biggest challenges with chemotherapy is the relative lack of discrimination between cancer and healthy tissue.
Novel linkers and connections for antibody–drug conjugates to treat cancer and infectious disease Antibody–drug conjugates (ADCs) are an exciting therapeutic, combining the extreme potency of a small molecule cytotoxic drug with the exquisite selectivity of a monoclonal antibody. Despite the promising concept and many decades of research and clinical experiments, only two ADCs are approved for human use.
Disulfide bonds provide a bioactivatable connection with applications in imaging and therapy. The circulation stability and intracellular release of disulfides are problematically coupled in that increasing stability causes a corresponding decrease in cleavage and payload release. However, an antibody offers the potential for a reversible stabilization. We examined this by attaching a small molecule directly to engineered cysteines in an antibody.
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