title: 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.
abstract: 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.
authors.affiliation: Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Jon N
authors.initials: JN
authors.lastname: Wesley
authors.forename: Edwin C
authors.initials: EC
authors.lastname: McGee
authors.forename: Kayhan
authors.initials: K
authors.lastname: Garmestani
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Yordanov
authors.forename: Chuanchu
authors.initials: C
authors.lastname: Wu
authors.forename: Otto A
authors.initials: OA
authors.lastname: Gansow
authors.forename: William C
authors.initials: WC
authors.lastname: Eckelman
authors.forename: John D
authors.initials: JD
authors.lastname: Bacher
authors.forename: Michael
authors.initials: M
authors.lastname: Flynn
authors.forename: Carolyn K
authors.initials: CK
authors.lastname: Goldman
authors.forename: Melvin
authors.initials: M
authors.lastname: MacLin
authors.forename: Uwe P
authors.initials: UP
authors.lastname: Schwartz
authors.forename: Terri
authors.initials: T
authors.lastname: Jackson-White
authors.forename: Celeste M
authors.initials: CM
authors.lastname: Phillip
authors.forename: Jean
authors.initials: J
authors.lastname: Decker
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Waldmann
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D021122:Protein Subunits; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D015375:Receptors, Interleukin-2; D001729:Bismuth; D001246:Astatine