Current and future applications of immunological attenuation via pegylation of cells and tissue

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.