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Keywords:

  • antibody-drug conjugate;
  • cytotoxic payload;
  • linker

With over 20 antibody-drug conjugates in clinical trials as well as a recently FDA-approved drug, it is clear that this is becoming an important and viable approach for selectively delivering highly cytotoxic agents to tumor cells while sparing normal tissue. This review discusses the critical aspects for this approach with an emphasis on the properties of the linker between the antibody and the cytotoxic payload that are required for an effective antibody-drug conjugate. Different linkers are illustrated with attention focused on (i) the specifics of attachment to the antibody, (ii) the polarity of the linker, (iii) the trigger on the linker that initiates cleavage from the drug, and (iv) the self-immolative spacer that liberates the active payload. Future directions in the field are proposed.