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.
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).
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.