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Developing an Antibody-Drug Conjugate Approach to Selective Inhibition of an Extracellular Protein.

ABSTRACT: Antibody-drug conjugates (ADCs) are a growing class of therapeutics that harness the specificity of antibodies and the cell-killing potency of small-molecule drugs. Beyond cytotoxics, there are few examples of the application of an ADC approach to difficult drug discovery targets. Here, we present the initial development of a non-internalising ADC, with a view to selectively inhibiting an extracellular protein. Employing the wellinvestigated matrix metalloproteinase-9 (MMP-9) as our model, we adapted a broad-spectrum, nonselective MMP inhibitor for conjugation and linked this to a MMP-9-targeting antibody. The resulting ADC fully inhibits MMP-9, and ELISA results suggest antibody targeting can direct a nonselective inhibitor.

SUBMITTER: Love EA

PROVIDER: S-EPMC6582441 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Developing an Antibody-Drug Conjugate Approach to Selective Inhibition of an Extracellular Protein.

Love Elizabeth A EA Sattikar Afrah A Cook Hannah H Gillen Kevin K Large Jonathan M JM Patel Seema S Matthews David D Merritt Andy A

Chembiochem : a European journal of chemical biology 20190207 6

Antibody-drug conjugates (ADCs) are a growing class of therapeutics that harness the specificity of antibodies and the cell-killing potency of small-molecule drugs. Beyond cytotoxics, there are few examples of the application of an ADC approach to difficult drug discovery targets. Here, we present the initial development of a non-internalising ADC, with a view to selectively inhibiting an extracellular protein. Employing the wellinvestigated matrix metalloproteinase-9 (MMP-9) as our model, we ad ...[more]

PMID: 30507063

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