Targeting Drug Conjugates To The Tumor Microenvironment: Probody Drug Conjugates
INNOVATIONS FOR NEXT-GENERATION ANTIBODY-DRUG CONJUGATES(2018)
摘要
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.
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关键词
Ab drug conjugate (ADC), Linker/payload, Linker/toxin, Toxicity, Mask, MMP9, pH, Probody, Protease, Tumor microenvironment
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