Antibody structure and engineering considerations for the design and function of Antibody Drug Conjugates (ADCs).

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Antibody structure and engineering considerations for the design and function of Antibody Drug Conjugates (ADCs).

Oncoimmunology. 2018;7(3):e1395127

Authors: Hoffmann RM, Coumbe BGT, Josephs DH, Mele S, Ilieva KM, Cheung A, Tutt AN, Spicer JF, Thurston DE, Crescioli S, Karagiannis SN

Abstract
Antibody-drug conjugates (ADCs) are emerging as effective tools in cancer therapy, combining the antibody's exquisite specificity for the target antigen-expressing cancer cell together with the cytotoxic potency of the payload. Much success stems from the rational design of "toxic warheads", chemically linked to antibodies, and from fine-tuning the intricate properties of chemical linkers. Here, we focus on the antibody moiety of ADCs, dissecting the impact of Fab, linkers, isotype and Fc structure on the anti-tumoral and immune-activating functions of ADCs. Novel design approaches informed by antibody structural attributes present opportunities that may contribute to the success of next generation ADCs.

PMID: 29375935 [PubMed]

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