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 Fc 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.
Sabatine
M S
MS
Transplantation Unit of the General Surgical Service, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Laufer
T
T
Glimcher
L H
LH
Widmer
M
M
Winn
H
H
Auchincloss
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics; D015316:Genetic Therapy; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006183:H-2 Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000627:therapeutic use*; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use; D012995:Solubility; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000637:transplantation
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D006183:H-2 Antigens; C108513:H-2A antigen; D007141:Immunoglobulin Fc Fragments; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins