Anitbody-drug conjugates

Overview

An antibody-drug conjugate (ADC) consists of a cytotoxin covalently linked to a monoclonal antibody (mAb) that recognizes an antigen differentially overexpressed on tumor cells.1 This allows for sensitive discrimination between malignant and healthy cells.1

ADCs Feature 3 Components1-3:

  1. Tumor-specific monoclonal antibody
  2. Toxin
  3. Linker
diagram

Therapeutic Potential

Treating cancer with cytotoxic agents introduces a risk of systemic adverse events.

Binding of the ADC to the recognized antigen triggers internalization and degradation of the mAb, which releases the cytotoxin inside the cell.

  • Key considerations in the development of ADC compounds include:
    • Target identification
    • Antibody engineering
    • Linker chemistry
    • Toxin selection
    • Clinical translation

Ideally, ADCs may help provide a wider therapeutic index with potentially fewer side effects than "free" cytotoxic agents.

  1. Bouchard H, Viskov C, Garcia-Echeverria C. Antibody-drug conjugates—a new wave of cancer drugs. Bioorg Med Chem Lett. 2014;24(23):5357-5363.
  2. Peters C, Brown S. Antibody-drug conjugates as novel anti-cancer chemotherapeutics. Biosci Rep. 2015;35(4):e00225. doi: 10.1042/BSR20150089.
  3. Diamantis N, Banerji U. Antibody-drug conjugates—an emerging class of cancer treatment. Br J Cancer. 2016;114(4):362-367.

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