Prolongation of cardiac allograft survival in murine recipients treated with a diphtheria toxin-related interleukin-2 fusion protein.
A diphtheria toxin-related IL-2 fusion gene has been constructed that encodes a 68KD recombinant toxin in which the diphtheria toxin receptor-binding domain has been replaced with amino acids 2-133 of IL-2. This chimeric IL-2 toxin is cytotoxic for cells expressing the high-affinity IL-2 receptor but not for cells lacking this receptor. The ability of this IL-2 toxin to prolong allograft survival was examined in a murine vascularized, heterotopic heart transplant model in the strain combination B10.BR into C57B1/10. When given at a dose of 1.0 micrograms/day for 10 days, the IL-2 toxin significantly prolonged allograft survival in all recipients. CRM-45, a fragment of diphtheria toxin missing the binding domain, was ineffective, confirming the specificity of the therapy. The results demonstrate that this IL-2 toxin, which targets activated T cells expressing the IL-2 receptor, will prolong allograft survival, offering a new option for immunosuppressive therapy.
Kirkman
R L
RL
Brigham and Women's Hospital, Boston, Massachusetts 02115.
Bacha
P
P
Barrett
L V
LV
Forte
S
S
Murphy
J R
JR
Strom
T B
TB
D000818:Animals; D000917:Antibody Formation; D004167:Diphtheria Toxin / Q000276:immunology / Q000493:pharmacokinetics / Q000633:toxicity; D006085:Graft Survival / Q000187:drug effects*; D006207:Half-Life; D016027:Heart Transplantation; D007376:Interleukin-2 / Q000276:immunology / Q000493:pharmacokinetics / Q000633:toxicity; D007668:Kidney / Q000187:drug effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000493:pharmacokinetics / Q000633:toxicity; D011994:Recombinant Proteins / Q000276:immunology / Q000493:pharmacokinetics / Q000633:toxicity
D004167:Diphtheria Toxin; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins