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

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.

SUBMITTER: Hoffmann RM

PROVIDER: S-EPMC5769674 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Hoffmann Ricarda M RM Coumbe Ben G T BGT Josephs Debra H DH Mele Silvia S Ilieva Kristina M KM Cheung Anthony A Tutt Andrew N AN Spicer James F JF Thurston David E DE Crescioli Silvia S Karagiannis Sophia N SN

Oncoimmunology 20171120 3

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 struct ...[more]

PMID: 29375935

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Considerations for the design of antibody drug conjugates (ADCs) for clinical development: lessons learned.

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