The anti-CD25 monoclonal antibody 7G7/B6, armed with the alpha-emitter 211At, provides effective radioimmunotherapy for a murine model of leukemia.
Radioimmunotherapy of cancer with radiolabeled antibodies has shown promise. alpha-Particles are very attractive for cancer therapy, especially for isolated malignant cells, as is observed in leukemia, because of their high linear energy transfer and short effective path length. We evaluated an anti-CD25 [interleukin-2 receptor alpha (IL-2R alpha)] monoclonal antibody, 7G7/B6, armed with (211)At as a potential radioimmunotherapeutic agent for CD25-expressing leukemias and lymphomas. Therapeutic studies were done in severe combined immunodeficient/nonobese diabetic mice bearing the karpas299 leukemia and in nude mice bearing the SUDHL-1 lymphoma. The results from a pharmacokinetic study showed that the clearance of (211)At-7G7/B6 from the circulation was virtually identical to (125)I-7G7/B6. The biodistributions of (211)At-7G7/B6 and (125)I-7G7/B6 were also similar with the exception of a higher stomach uptake of radioactivity with (211)At-7G7/B6. Therapy using 15 microCi of (211)At-7G7/B6 prolonged survival of the karpas299 leukemia-bearing mice significantly when compared with untreated mice and mice treated with (211)At-11F11, a radiolabeled nonspecific control antibody (P < 0.01). All of the mice in the control and (211)At-11F11 groups died by day 46 whereas >70% of the mice in the (211)At-7G7/B6 group still survived at that time. In summary, (211)At-7G7/B6 could serve as an effective therapeutic agent for patients with CD25-expressing leukemias.
Zhang
Meili
M
Metabolism Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-1374, USA.
Yao
Zhengsheng
Z
Zhang
Zhuo
Z
Garmestani
Kayhan
K
Talanov
Vladimir S
VS
Plascjak
Paul S
PS
Yu
Sarah
S
Kim
Hyung-Sik
HS
Goldman
Carolyn K
CK
Paik
Chang H
CH
Brechbiel
Martin W
MW
Carrasquillo
Jorge A
JA
Waldmann
Thomas A
TA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D015458:Leukemia, T-Cell / Q000276:immunology* / Q000532:radiotherapy; D008223:Lymphoma / Q000276:immunology / Q000532:radiotherapy; D051379:Mice; D008819:Mice, Nude; D016499:Radioimmunotherapy; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D053645:Interleukin-2 Receptor alpha Subunit