(452c) Erythrocytes As Carriers of Immunoglobulin Based Therapeutic Drugs

Erythrocytes as
Carriers of Immunoglobulin Based Therapeutic Drugs

Weihang Ji, Richard R. Koepsel, Jill D.
Andersen, Sheiliza Carmali and Alan J. Russell*

Disruptive Health Technology
Institute, Carnegie Mellon University

5000 Forbes Ave, Pittsburgh, PA
15213

*Email address: alanrussell@cmu.edu

ABSTRACT

The spectacular success of immunoglobulin-based
therapeutics in treating a wide range of diseases has heightened the need to
further enhance their efficacy and lifetime, while diminishing any deleterious
side effects. We have explored a range of chemistries that allow us to couple
antibodies to red blood cells.  The couplings can enable controlled
delivery from the cell surface to plasma or the antibody can remain permanently
attached to the membrane.  For all methods we can attach on the order of
10⁵ antibodies per red blood cell (human and rat) and these
cell-displayed antibody arrays were shown to be stable in physiological buffer
for more than 60 days.  In a rodent model, our preliminary results showed
that erythrocytes with arrays of antibodies were stable and functional.  We
are currently investigating the impact of covalently attaching antibody arrays on
the circulation lifetime and the antigen-scavenging efficiency of red blood
cells in a rat model. In summary, we believe that using our bioconjugation
strategies, we could build a potentially
long-lived, biocompatible functional red blood cell that could efficiently remove
antigens from circulation.

The authors would like to thank
the Institute of Transfusion Medicine (ITxM, Pittsburgh, PA) for funding this
work. We also gratefully acknowledge the Central Blood Bank (Pittsburgh, PA)
for their supply of healthy erythrocytes.

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