Scott Laboratory - Immios Biologics

Scott Laboratory Website

Canadian Blood Service • University of British Columbia • Centre for Blood Research • Vancouver, BC  Canada

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Polymer-Based Bioengineering Solutions for Immune Modulation and the Prophylactic Inhibition of Viral Infections

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Stealth RBC:  Boutique RBC For the Discriminating Customer

Immunocamouflaged (Stealth) RBC: Alloimmunization to non-ABO Blood Group Antigens is a significant problem in transfusion medicine - especially in the chronically transfused patient.  Our goals for the Stealth RBC:

•  Compassionate Use in  Alloimmunized Patients With ‘RARE’ Blood Types

•  Prophylactic Use in At-Risk Individuals - Especially Chronically Transfused Individuals

•  Meeting transfusion needs in Remote and/or Blood Supply Constrained Locations.

•  Improved Supply of RhD‘who cares’ RBC (i.e., camouflaged RhD+) in low frequency countries (e.g., China).  Predictive Mapping Studies suggests that PEGylated RhD+ RBC would be safe in both naive and alloimunized RhD- recipients.

Relevant Publications

Scott, M.D., Murad, K.L., Koumpouras, F., Talbot, M., and Eaton, J.W.  Chemical camouflage of antigenic determinants:  “Stealth” erythrocytes.  Proc. Nat. Acad. Sci. USA, 94:7566-7571(1997).

Scott, M.D. and Murad, K.L.  Cellular camouflage:  Fooling the immune system with polymers.  Current Pharmaceutical Design, 4:423-438(1998).

Murad, K.L., Mahany, K.L.  Kuypers, F.A., Brugnara, C., Eaton, J.W, and Scott, M.D.  Structural and functional consequences of antigenic modulation of red cells with methoxypoly(ethylene glycol).  Blood, 93:2121-2127(1999).

Scott, M.D. Bradley, A.J., and Murad, K.L.  Camouflaged Blood Cells:  Low technology bioengineering for transfusion medicine? Transfusion Medicine Reviews, 14:53-63.(2000)

Chen, A.M. and Scott, M.D.  Current and Future Applications of Immunologic Attenuation Via PEGylation of Cells and Tissues.  BioDrugs, 15:833-847(2001).

Bradley, A.J. Test, T.T., Murad, K.L., Mitsuyoshi, J. and  Scott, M.D.  Interactions of IgM ABO Antibodies and complement with methoxy-PEG-modified human RBCs.  Transfusion, 41:1225-1233(2001).

Bradley, A.J., Murad, K.L., Regan, K.L., and Scott, M.D.  Biophysical consequences of linker chemistry and polymer size on stealth erythrocytes:  Size does matter.  Biochimica et Biophysica Acta,  1561:147-58(2002).

Chen, A.M. and Scott, M.D.  Immunocamouflage:  Prevention of transfusion-induced graft-versus-host disease via polymer grafting of donor cells.  Journal of Biomedical Materials Research,  67A:626-636(2003).

Scott, M.D. Bradley, A.J., and Murad, K.L.  Stealth Erythrocytes:  Effects of polymer grafting on biophysical, biological and immunological parameters.  Blood Transfusion, 1(3):245-266(2003).

Bradley, A.J. and Scott, M.D.  Separation and purification of methoxypoly(ethylene glycol) grafted red blood cells via two-phase partitioning.  J. Chromatogr. B., 807:163-168 (2004).

Chen, A.M. and Scott, M.D.  Immunocamouflage:  Comparative analysis of polymer and linker chemistries on the efficacy of immunocamoulfage of murine cells.  Artificial Cells, Blood Substitutes, and Biotechnology, 34:305-322(2006).

Bradley, A.J. and Scott, M.D.  Immune complex binding by immunocamouflaged [poly(ethylene glycol)] erythrocytes.  Am. J. Hematology, 82:970-975(2007).

Le, Y. and Scott, M.D. Immunocamouflage: The Biophysical Basis of Immunoprotection by Grafted Methoxypoly(Ethylene Glycol) [mPEG].  Acta Biomaterialia, 6:2631-2641 (2010).

Wang, D., Kyluik, D.L, Murad, K.L., Toyofuku, W.M., and Scott, M.D.  Polymer-Mediated Immunocamouflage of Red Blood Cells: Effects of Polymer Size on Antigenic and Immunogenic Recognition of Allogeneic Donor Blood Cells. Science China – Life Sciences, 54:589-598 (2011).  [NOTE:  Cover Art and featured article]

Wang, D., Toyofuku, W.M., Scott, M.D. The Potential Utility of Methoxypoly(Ethylene Glycol)-Mediated Prevention of Rhesus Blood Group Antigen RhD Recognition in Transfusion Medicine.  Biomaterials, 33:3002-3012. (2012)

Le, Y. Li, L., Wang, D. and Scott, M.D. Immunocamouflage of Latex Surfaces by Grafted Methoxypoly(Ethylene Glycol) [mPEG]:  Proteomic Analysis of Plasma Protein Adsorption. Science China - Life Sciences, 55:191-201 (2012).  [NOTE:  Cover Art and featured article]

Kyluik-Price D.L., Li, L. and Scott, M.D.  Comparative Efficacy of Blood Cell Immunocamouflage by Membrane Grafting of Methoxypoly(Ethylene Glycol) and Polyethyloxazoline.  Biomaterials 35(1):412-422 (2014).

Li, L., Noumsi, G.T., Kwok, Y.Y.E., Moulds, J.M. and Scott, M.D.  Inhibition of Phagocytic Recognition of Anti-D Opsonized Rh D+ RBC By Polymer-Mediated Immunocamouflage.  American Journal of Hematology, 90(12):1165-1170 (2015).

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  Stealth RBC Research

Scanning EM of a polymer-modified RBC.  Shows normal discoid morphology.

RhD+ red blood cells are effectively camouflaged from phagocytic recognition.  Shown is the phagocytosis of unmodied and mPEG-modified RhD+ RBC opsonized with 8 human sourced anti-D alloantibodies using the clinically validated monocyte-monolayer assay (MMA).  Note the effect of polymer size (2, 5 and 20 kDa) on the induction of immunocamouflage.

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