Systemic radioimmunotherapy using a monoclonal antibody, anti-Tac directed toward the alpha subunit of the IL-2 receptor armed with the alpha-emitting radionuclides (212)Bi or (211)At.
To exploit the fact that IL-2 receptors are expressed by T-cells responding to foreign antigens but not by resting T-cells, humanized anti-Tac (HAT) armed with alpha-emitting radionuclides (212)Bi and (211)At was evaluated in a cynomolgus cardiac allograft model. Control graft survival was 8.2+/- 0.5 days compared with 14.0+/-1.3 days (p<0.01) survival for monkeys treated with (212)Bi labeled HAT and 26.7+/-2.4 days survival (p<0.001 versus controls) with (211)At labeled HAT. Thus, (211)At labeled HAT may have application in organ transplantation and in treatment of IL-2 receptor expressing T-cell leukemia.
Wesley
Jon N
JN
Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
McGee
Edwin C
EC
Garmestani
Kayhan
K
Brechbiel
Martin W
MW
Yordanov
Alexander T
AT
Wu
Chuanchu
C
Gansow
Otto A
OA
Eckelman
William C
WC
Bacher
John D
JD
Flynn
Michael
M
Goldman
Carolyn K
CK
MacLin
Melvin
M
Schwartz
Uwe P
UP
Jackson-White
Terri
T
Phillip
Celeste M
CM
Decker
Jean
J
Waldmann
Thomas A
TA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D001246:Astatine / Q000276:immunology / Q000627:therapeutic use*; D001729:Bismuth / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control / Q000532:radiotherapy*; D006085:Graft Survival / Q000276:immunology; D008252:Macaca fascicularis; D051379:Mice; D008819:Mice, Nude; D021122:Protein Subunits; D016499:Radioimmunotherapy / Q000379:methods*; D011868:Radioisotopes / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000276:immunology / Q000627:therapeutic use; D015375:Receptors, Interleukin-2 / Q000276:immunology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D021122:Protein Subunits; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D015375:Receptors, Interleukin-2; D001729:Bismuth; D001246:Astatine