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Payload diversification: a key step in the development of antibody-drug conjugates.

ABSTRACT: Antibody-drug conjugates (ADCs) is a fast moving class of targeted biotherapeutics that currently combines the selectivity of monoclonal antibodies with the potency of a payload consisting of cytotoxic agents. For many years microtubule targeting and DNA-intercalating agents were at the forefront of ADC development. The recent approval and clinical success of trastuzumab deruxtecan (Enhertu^®) and sacituzumab govitecan (Trodelvy^®), two topoisomerase 1 inhibitor-based ADCs, has shown the potential of conjugating unconventional payloads with differentiated mechanisms of action. Among future developments in the ADC field, payload diversification is expected to play a key role as illustrated by a growing number of preclinical and clinical stage unconventional payload-conjugated ADCs. This review presents a comprehensive overview of validated, forgotten and newly developed payloads with different mechanisms of action.

SUBMITTER: Conilh L

PROVIDER: S-EPMC9847035 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Payload diversification: a key step in the development of antibody-drug conjugates.

Conilh Louise L Sadilkova Lenka L Viricel Warren W Dumontet Charles C

Journal of hematology & oncology 20230117 1

Antibody-drug conjugates (ADCs) is a fast moving class of targeted biotherapeutics that currently combines the selectivity of monoclonal antibodies with the potency of a payload consisting of cytotoxic agents. For many years microtubule targeting and DNA-intercalating agents were at the forefront of ADC development. The recent approval and clinical success of trastuzumab deruxtecan (Enhertu<sup>®</sup>) and sacituzumab govitecan (Trodelvy<sup>®</sup>), two topoisomerase 1 inhibitor-based ADCs, h ...[more]

PMID: 36650546

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