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Isolation and Characterization Of Chimeric Human Fc-expressing Proteins Using Protein A Membrane Adsorbers And A Streamlined Workflow
Published on: January 8, 2014
Predilution hemofiltration for the removal of protein bound antigens
1Division of Artificial Organs, University of Utah, Salt Lake City 84112.
Abstract:
In cancer, tumor antigen (Ag) and the antigen-antibody immune complexes (IC) have been implicated with the inhibition of macrophage or lymphocyte function, interleukin generation and induction of suppressor cells and immunosuppressants. Plasma exchange depletes both Ag and antibodies (Ab) from the circulation. However, the Abs might be cytotoxic to cancer cells. Hence, a better treatment would be to remove the Ag without depleting the Abs. Such a procedure involves dissociation of Ag from Ab either by a change in pH of the plasma or by a hemodilution of the blood followed by removal of both the free and the dissociated Ag by ultrafiltration. The present work presents a theoretical analysis of the predilution hemofiltration system designed to remove the antigens which are weakly bound to proteins. A single pool model for the patient was assumed. The variables which effect the clearance of Ag are the protein binding constant (K), the extent of dilution of blood, the initial ratio between Ag and Ab concentrations. A computer simulation of the derived mass balance equations shows that the clearance of total Ag from the plasma pool decreases with (i) increase in the value of K, but it can be off set by increasing the extent of hemodilution, and (ii) decrease in initial Ag/Ab ratio, but this effect can be minimized by increasing the hemodilution fluid flow rate.
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