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 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.
Thurber
Greg M
GM
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Schmidt
Michael M
MM
Wittrup
K Dane
KD
D000906:Antibodies / Q000008:administration & dosage / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015195:Drug Design; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D010539:Permeability; D014018:Tissue Distribution
D000906:Antibodies; D000970:Antineoplastic Agents