Delayed rejection of soluble tumor necrosis factor receptor-secreting tumor allografts

Background. Exogenous soluble tumor necrosis factor receptor (TNFR) has been shown to be an effective immunosuppressant. It has yet to be tested whether tissues secreting soluble TNFR, when transplanted into a foreign host, could locally generate immunosuppression and therefore manifest prolonged survival. Methods. A murine tumor line was transfected with the gene encoding a chimeric protein consisting of the extracellular domain of the human 75-kDa TNFR fused to the Pc region of the human IgG1 heavy chain. This tumor line was then injected into allogeneic recipients. Results. Transfected tumor cells were shown to secrete soluble TNFR. When transplanted into minor histocompatibility antigen-disparate allogeneic recipients, these tumor cells grew as a solid tumor and resisted rejection, whereas untransfected tumors and interleukin-4 receptor transfectant controls were rejected within 4 weeks. The resistance to rejection could be reversed by coadministration of an anti-TNFR monoclonal antibody. Conclusions, Prolongation of graft survival can be achieved by genetically altering transplanted tissue to secrete soluble cytokine receptors.