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A mechanistic compartmental model for total antibody uptake in tumors
Name
nihms-405659.pdf
Description
Accepted version
Size
848.63 KB
Format
Adobe PDF
Checksum (MD5)
fce8d94e23d1891ef54b2a238a39306b
Author(s)
Thurber, Greg M
Dane Wittrup, K
Date Issued
2012
Journal
Journal of Theoretical Biology
Publisher
Elsevier BV
Citation
Thurber, G. M., and K. Dane Wittrup. "A Mechanisti Compartmental Model for Total Antibody Uptake in Tumors." J Theor Biol (2012).
Version
Author's final manuscript
Abstract
Antibodies are under development to treat a variety of cancers, such as lymphomas, colon, and breast cancer. A major limitation to greater efficacy for this class of drugs is poor distribution in vivo. Localization of antibodies occurs slowly, often in insufficient therapeutic amounts, and distributes heterogeneously throughout the tumor. While the microdistribution around individual vessels is important for many therapies, the total amount of antibody localized in the tumor is paramount for many applications such as imaging, determining the therapeutic index with antibody drug conjugates, and dosing in radioimmunotherapy. With imaging and pretargeted therapeutic strategies, the time course of uptake is critical in determining when to take an image or deliver a secondary reagent. We present here a simple mechanistic model of antibody uptake and retention that captures the major rates that determine the time course of antibody concentration within a tumor including dose, affinity, plasma clearance, target expression, internalization, permeability, and vascularization. Since many of the parameters are known or can be estimated in vitro, this model can approximate the time course of antibody concentration in tumors to aid in experimental design, data interpretation, and strategies to improve localization.
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
10.1016/j.jtbi.2012.08.034
