Practical Theoretic Guidance for the Design of Tumor-Targeting Agents
Name
Wittrup_Practical theoretic.pdf
Size
1.72 MB
Format
Adobe PDF
Checksum (MD5)
49ee55a2cab6ecd22fcdeb4b879dd6a5
Author(s)
Thurber, Greg M.
Schmidt, Michael M.
Rhoden, John J.
Wittrup, Karl Dane
Date Issued
2012
Journal
Protein Engineering for Therapeutics, Part B
Publisher
Elsevier
Citation
Wittrup, K. Dane, Greg M. Thurber, Michael M. Schmidt, and John J. Rhoden. “Practical Theoretic Guidance for the Design of Tumor-Targeting Agents.” Protein Engineering for Therapeutics, Part B (2012): 255–268.
Version
Author's final manuscript
Abstract
Theoretical analyses of targeting agent pharmacokinetics provides specific guidance with respect to desirable design objectives such as agent size, affinity, and target antigen. These analyses suggest that IgG-sized macromolecular constructs exhibit the most favorable balance between systemic clearance and vascular extravasation, resulting in maximal tumor uptake. Quantitative predictions of the effects of dose and binding affinity on tumor uptake and penetration are also provided. The single bolus dose required for saturation of xenografted tumors in mice can be predicted from knowledge of antigen expression level and metabolic half-life. The role of high binding affinity in tumor uptake can be summarized as: essential for small peptides, less important for antibodies, and negligible for nanoparticles.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/b978-0-12-396962-0.00010-0
