The antibody-drug conjugate: an enabling modality for natural product-based cancer therapeutics
Nat. Prod. Rep., 2013, 30,625-639
DOI: 10.1039/C3NP20113A, Review Article
DOI: 10.1039/C3NP20113A, Review Article
Hans-Peter Gerber, Frank E. Koehn, Robert T. Abraham
In this review, we discuss recent advances related to the construction of ADCs,
In this review, we discuss recent advances related to the construction of ADCs,
the optimization of ADC safety and efficacy, and the increasingly pivotal roles of
natural product payloads in the current and future landscape of ADC therapy.
The Antibody Drug Conjugate (ADC) is a therapeutic modality consisting of a monoclonal antibody
attached to a cytotoxic, small-molecule payload. The antibody portion of the ADC serves as a
transport vehicle that recognizes and binds to a protein antigen expressed in tumor tissues.
The localized delivery and release of the payload within or near malignant cells allows for targeted
delivery of a potent cytotoxic agent to diseased tissue, while reducing damage to antigen-negative,
normal tissues. Recent years have witnessed an explosive increase in ADC-based therapies,
due mainly to clinical reports of activity in both hematologic and epithelial cancers.
Accompanying this upsurge in ADC development is a renewed interest in natural product cytotoxins,
which are typically highly potent cell-killing agents, but suffer from poor drug-like properties and
narrow safety margins when systemically administered as conventional chemotherapeutics.
In this review, we discuss recent advances related to the construction of ADCs,
the optimization of ADC safety and efficacy, and the increasingly pivotal roles of
natural product payloads in the current and future landscape of ADC therapy.
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