Chimeric Small Antibody Fragments as Strategy to Deliver Therapeutic Payloads

Publication date: Available online 6 April 2018 Source:Advances in Protein Chemistry and Structural Biology Author(s): Sandra Aguiar, Joana Dias, Ana M. Manuel, Roberto Russo, Pedro M.P. Gois, Frederico A. da Silva, Joao Goncalves Antibody–drug conjugates (ADCs) represent an innovative class of biopharmaceuticals, which aim at achieving a site-specific delivery of cytotoxic agents to the target cell. The use of ADCs represents a promising strategy to overcome the disadvantages of conventional pharmacotherapy of cancer or neurological diseases, based on cytotoxic or immunomodulatory agents. ADCs consist of monoclonal antibodies attached to biologically active drugs by means of cleavable chemical linkers. Advances in technologies for the coupling of antibodies to cytotoxic drugs promise to deliver greater control of drug pharmacokinetic properties and to significantly improve pharmacodelivery applications, minimizing exposure of healthy tissue. The clinical success of brentuximab vedotin and trastuzumab emtansine has led to an extensive expansion of the clinical ADC pipeline. Although the concept of an ADC seems simple, designing a successful ADC is complex and requires careful selection of the receptor antigen, antibody, linker, and payload. In this review, we explore insights in the antibody and antigen requirements needed for optimal payload delivery and support the development of novel and improved ADCs for the treatment of cancer and neurological diseas...
Source: Advances in Protein Chemistry and Structural Biology - Category: Biochemistry Source Type: research