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Current and Future Applications of Immunological Attenuation via Pegylation of Cells and Tissue

BioDrugs volume 15, pages 833–847 (2001)Cite this article

Abstract

Prevention of immunological rejection of transplanted tissues is of crucial importance in transplantation medicine. Current procedures primarily use pharmacological agents such as cyclosporin, which, while effective, must be typically administered for the life of the individual. Furthermore, the drug-induced global immunosuppression of the patient predisposes the individual to infection and enhances their risk of developing certain forms of cancer. Hence, additional methods are needed to both enhance tissue engraftment and diminish the adverse effects of current immunosuppressive therapy. Studies from blood transfusion (i.e. a specialised form of cellular transplantation) suggest that covalent modification of cells and tissues with methoxypoly(ethylene glycol) [mPEG] can significantly diminish rejection episodes and may further enhance the induction of tolerance to donor tissues. The mechanisms underlying mPEG-mediated immunocamouflage are the loss of antigen recognition, impaired cell-cell interaction, and an inability of endogenous antibodies (e.g. immunoglobulin G) to effectively recognise and bind foreign epitopes. As a consequence of the global camouflage imparted by mPEG, the weak co-stimulation of alloreactive T cells may subsequently induce apoptosis, thus leading to tolerance. Initial studies on the transplantation of pegylated isogeneic rat pancreatic islets demonstrates that mPEG-derivatisation does not impair in vivo cellular signalling and function. Thus, in contrast to the pharmacological inhibition of the recipient’s immune response, the mPEG-mediated immunocamouflage directly addresses the inherent antigenicity and immunogenicity of the donor tissue itself while leaving the recipient a fully competent immune system.

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Acknowledgements

We acknowledge Katy L. Regan, Albany Medical College, Dr Kari L. Murad, College of St. Rose, and Dr Amanda J. Bradley, Canadian Blood Services, for their ongoing contributions to this work. In addition, we are indebted to Dr Bernhard J. Hering, Director of Islet Transplantation, Diabetes Institute for Immunology and Transplantation, University of Minnesota. The research described is supported by National Institutes of Health Grant HL58584. This work was completed in partial fulfilment of a doctoral thesis (by Audrey M. Chen) to fulfil the requirements of the Graduate Program in Immunology and Microbial Disease at the Albany Medical College.

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  1. Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA

    Audrey M. Chen &  Mark D. Scott

  2. Department of Pathology and Laboratory Medicine, Canadian Blood Services, Koerner Pavilion, UBC Hospital, University of British Columbia, 2211 Westbrook Mall, Vancouver, B.C., Canada, V6T 2B5

    Mark D. Scott

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  1. Audrey M. Chen
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Correspondence to Mark D. Scott.

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Chen, A.M., Scott, M.D. Current and Future Applications of Immunological Attenuation via Pegylation of Cells and Tissue. BioDrugs 15, 833–847 (2001). https://doi.org/10.2165/00063030-200115120-00005

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  • DOI: https://doi.org/10.2165/00063030-200115120-00005

Keywords

  • Major Histocompatibility Complex Class
  • Graft Versus Host Disease
  • Donor Tissue
  • Human Leucocyte Antigen
  • Chronic Host Versus Graft Disease