Targeting Drug Conjugates to the Tumor Microenvironment: Probody Drug Conjugates

  • Jack LinEmail author
  • Jason Sagert
Part of the Cancer Drug Discovery and Development book series (CDD&D)


The tolerability and ultimately efficacy of ADCs are limited by 2 major issues: (1) antigen expression that is too low on tumors, resulting in insufficient toxin delivery to the tumor, especially within the confines of the clinical MTD established by linker/payload-driven off-target toxicity and (2) too much antigen expression on normal healthy tissues, resulting in on-target but off-tumor toxicity. In this chapter, we will review strategies for making antibody prodrugs that have been or could be used to selectively deliver drug to a tumor compared to normal tissues. These technologies have the potential to lower on-target, off-tumor toxicities and enable better efficacy of ADCs due to better target selection and the delivery of higher concentrations of drug to tumors.


Ab drug conjugate (ADC) Linker/payload Linker/toxin Toxicity Mask MMP9 pH Probody Protease Tumor microenvironment 


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.CytomX Therapeutics, Inc.South San FranciscoUSA

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