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Antibodies 2019, 8(1), 3; https://doi.org/10.3390/antib8010003

Pharmacologic Considerations in the Disposition of Antibodies and Antibody-Drug Conjugates in Preclinical Models and in Patients

1
University of North Carolina (UNC), Eshelman School of Pharmacy, Chapel Hill, NC 27599, USA
2
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
3
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
*
Author to whom correspondence should be addressed.
Received: 30 November 2018 / Revised: 21 December 2018 / Accepted: 22 December 2018 / Published: 1 January 2019
(This article belongs to the Special Issue Antibody-Drug Conjugate)
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Abstract

The rapid advancement in the development of therapeutic proteins, including monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs), has created a novel mechanism to selectively deliver highly potent cytotoxic agents in the treatment of cancer. These agents provide numerous benefits compared to traditional small molecule drugs, though their clinical use still requires optimization. The pharmacology of mAbs/ADCs is complex and because ADCs are comprised of multiple components, individual agent characteristics and patient variables can affect their disposition. To further improve the clinical use and rational development of these agents, it is imperative to comprehend the complex mechanisms employed by antibody-based agents in traversing numerous biological barriers and how agent/patient factors affect tumor delivery, toxicities, efficacy, and ultimately, biodistribution. This review provides an updated summary of factors known to affect the disposition of mAbs/ADCs in development and in clinical use, as well as how these factors should be considered in the selection and design of preclinical studies of ADC agents in development. View Full-Text
Keywords: Antibody-drug conjugates; Pharmacology; Mononuclear phagocyte system; Pharmacokinetics; Therapeutic proteins Antibody-drug conjugates; Pharmacology; Mononuclear phagocyte system; Pharmacokinetics; Therapeutic proteins
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Lucas, A.T.; Robinson, R.; Schorzman, A.N.; Piscitelli, J.A.; Razo, J.F.; Zamboni, W.C. Pharmacologic Considerations in the Disposition of Antibodies and Antibody-Drug Conjugates in Preclinical Models and in Patients. Antibodies 2019, 8, 3.

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