title: A biophysical model of cell adhesion mediated by immunoadhesin drugs and antibodies.
abstract: A promising direction in drug development is to exploit the ability of natural killer cells to kill antibody-labeled target cells. Monoclonal antibodies and drugs designed to elicit this effect typically bind cell-surface epitopes that are overexpressed on target cells but also present on other cells. Thus it is important to understand adhesion of cells by antibodies and similar molecules. We present an equilibrium model of such adhesion, incorporating heterogeneity in target cell epitope density, nonspecific adhesion forces, and epitope immobility. We compare with experiments on the adhesion of Jurkat T cells to bilayers containing the relevant natural killer cell receptor, with adhesion mediated by the drug alefacept. We show that a model in which all target cell epitopes are mobile and available is inconsistent with the data, suggesting that more complex mechanisms are at work. We hypothesize that the immobile epitope fraction may change with cell adhesion, and we find that such a model is more consistent with the data, although discrepancies remain. We also quantitatively describe the parameter space in which binding occurs. Our model elaborates substantially on previous work, and our results offer guidance for the refinement of therapeutic immunoadhesins. Furthermore, our comparison with data from Jurkat T cells also points toward mechanisms relating epitope immobility to cell adhesion.
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona, United States of America.
authors.forename: Ryan N
authors.initials: RN
authors.lastname: Gutenkunst
authors.forename: Daniel
authors.initials: D
authors.lastname: Coombs
authors.forename: Toby
authors.initials: T
authors.lastname: Starr
authors.forename: Michael L
authors.initials: ML
authors.lastname: Dustin
authors.forename: Byron
authors.initials: B
authors.lastname: Goldstein
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D002448:Cell Adhesion / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells / Q000166:cytology; D008954:Models, Biological; D008962:Models, Theoretical
chemical_list: D000911:Antibodies, Monoclonal