Cardiac allograft survival in mice treated with IL-2-PE40.
IL-2-PE40 is a chimeric protein composed of human interleukin 2 (IL-2) genetically fused to the amino terminus of a modified form of Pseudomonas exotoxin lacking its cell recognition domain. IL-2-PE40, which is extremely cytotoxic to IL-2 receptor-positive cells, was examined for its ability to prevent graft rejection in mice in which activation of T cells is prominent. We demonstrate that intraperitoneally administered IL-2-PE40 specifically and significantly prolongs the survival of vascularized heart allografts in mice. The chimeric toxin, IL-2-PE40, offers an alternative approach to the treatment of autoimmune diseases and transplant rejection in humans.
Lorberboum-Galski
H
H
Laboratory of Molecular Biology, National Institutes of Health, Bethesda, MD 20892.
Barrett
L V
LV
Kirkman
R L
RL
Ogata
M
M
Willingham
M C
MC
FitzGerald
D J
DJ
Pastan
I
I
D036002:ADP Ribose Transferases; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001427:Bacterial Toxins; D005098:Exotoxins / Q000235:genetics / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D006321:Heart / Q000187:drug effects; D016027:Heart Transplantation; D000922:Immunotoxins; D007376:Interleukin-2 / Q000235:genetics / Q000494:pharmacology* / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D011994:Recombinant Proteins; D014184:Transplantation, Homologous; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D007376:Interleukin-2; D007770:L-Lactate Dehydrogenase; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C057961:IL-2-PE40 chimeric protein, recombinant