Use of an Immunoisolation Device for Cell Transplantation and Tumor Immunotherapy

Immunoisolation, or implantation of tissues in a membrane-enclosed device, is an approach aimed at allowing maintenance of cells in an environment where they are segregated from the host tissues. The transplant device must be well vascularized to support the implanted cells at high densities. Further, encapsulated allogeneic tissues can be protected from immune attack without the need for immunosuppression. Early work on immunoisolation, by Algire and co-workers, showed that allografts could be protected when implanted into mice within diffusion chambers with large pore membranes that prevented entry of host We have had similar result^.^ Rejection of allografts occurred only if the pores were sufficiently large to allow entry of host cells. Over the last decade several groups have investigated immunoisolation using a variety of approaches. Hollow fiber filters have been shown to protect pancreatic islet xenografts in rats' and mice.' However, these devices utilize low flux membranes that prohibit the implantation of high desities of islets.' Another approach is to implant microcapsules of alginate and other hydrogels.' This approach has been shown to be effective in many laboratories; however, the capsules are irretrievable after implantation in the peritoneal cavity and are highly fragile.1° Moreover, rejection responses including severe fibrotic responses were observed whenever microcapsules either empty or containing xenogeneic islets became overgrown or attached to host tissues."-'4 We have developed a flat sheet immunoisolation device called the TheraCyterH system (FIG. 1). The membranes of this device protect allogeneic tissues at high densities' but are unable to protect xenogeneic cells from destruction.'.Is In addition to using the TheraCyte'" system to protect encapsulated tissues from immune destruction, we have taken the unique approach of using the device to deliver antigenic stimuli in order to deliberately induce an immune response outside of the device directed at the destruction of tumor cells. The present manuscript discusses several aspects of the TheraCyte" system including device vascularization, the immunology of transplantation of allografts and xenografts, and the use of the device for the treatment of cancer.