Factors determining antibody distribution in tumors

The development of antibody therapies for cancer is increasing rapidly, primarily owing to their specificity. Antibody distribution in tumors is often extremely uneven, however, leading to some malignant cells being exposed to saturating concentrations of antibody, whereas others are completely unta...

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Bibliographic Details
Published in:Trends in pharmacological sciences (Regular ed.) 2008-02, Vol.29 (2), p.57-61
Main Authors: Thurber, Greg M, Schmidt, Michael M, Wittrup, K. Dane
Format: Article
Language:English
Subjects:
Advanced Basic Science
Antibodies - administration & dosage
Antibodies - metabolism
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - pharmacokinetics
Drug Design
Humans
Models, Biological
Neoplasms - drug therapy
Neoplasms - immunology
Permeability
Tissue Distribution
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Summary:The development of antibody therapies for cancer is increasing rapidly, primarily owing to their specificity. Antibody distribution in tumors is often extremely uneven, however, leading to some malignant cells being exposed to saturating concentrations of antibody, whereas others are completely untargeted. This is detrimental because large regions of cells escape therapy, whereas other regions might be exposed to suboptimal concentrations that promote a selection of resistant mutants. The distribution of antibody depends on a variety of factors, including dose, affinity, antigens per cell and molecular size. Because these parameters are often known or easily estimated, a quick calculation based on simple modeling considerations can predict the uniformity of targeting within a tumor. Such analyses should enable experimental researchers to identify in a straightforward way the limitations in achieving evenly distributed antibody, and design and test improved antibody therapeutics more rationally.
ISSN:0165-6147
1873-3735
DOI:10.1016/j.tips.2007.11.004