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Adv Protein Chem Struct Biol. 2018;112:143-182. doi: 10.1016/bs.apcsb.2018.03.002. Epub 2018 Apr 6.

Chimeric Small Antibody Fragments as Strategy to Deliver Therapeutic Payloads.

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Centro de Investigação Interdisciplinar em Sanidade Animal (CIISA), Faculdade de Medicina Veterinária, Universidade de Lisboa, Avenida da Universidade Técnica, Lisboa, Portugal.
iMed.ULisboa-Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal.
iMed.ULisboa-Research Institute for Medicines, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal. Electronic address:


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 diseases.


Antibody engineering; Antibody–drug conjugates; Bioorganic chemistry; Oncology and CNS diseases; Payload conjugation; Small domain antibodies; Targeted drug delivery

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