Preclinical evaluation of an anti-CD25 monoclonal antibody, 7G7/B6, armed with the beta-emitter, yttrium-90, as a radioimmunotherapeutic agent for treating lymphoma.
OBJECTIVE
Radioimmunotherapy of cancer with radiolabeled antibodies has shown promise. We evaluated an anti-CD25 monoclonal Antibody, 7G7/B6, armed with (90)Y as a potential radioimmunotherapeutic agent for CD25-expressing lymphomas.


METHODS
The lymphoma model was established by subcutaneous injection of 1 x 10(7) SUDHL-1 cells into nude mice. The biodistribution of (111)In-7G7/B6 and therapeutic studies with (90)Y-7G7/B6 were performed in the tumor-bearing mice.


RESULTS
Therapy using (90)Y-7G7/B6 prolonged survival of the SUDHL-1 lymphoma-bearing mice significantly, as compared with either untreated mice or the mice treated with (90)Y-11F11, a radiolabeled isotype-matched control antibody (p < 0.001). All of the mice in the control and the (90)Y-11F11 treatment groups died by days 18 and 24, respectively. In contrast, 30% of the mice in the low-dose group (75 microCi of (90)Y-7G7/B6/mouse) and 75% in the high-dose group (150 microCi of (90)Y-7G7/B6/mouse) became tumor free and remained healthy for greater than 6 months.


CONCLUSIONS
Our findings suggested that (90)Y-7G7/B6 is a potentially useful radioimmunotherapeutic agent for the treatment of patients with CD25-expressing lymphomas.
Zhang
Meili
M
Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1374, USA.
Yao
Zhengsheng
Z
Garmestani
Kayhan
K
Yu
Sarah
S
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 / Q000276:immunology / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D061067:Antibodies, Monoclonal, Humanized; D000918:Antibody Specificity / Q000276:immunology; D045744:Cell Line, Tumor; D000077561:Daclizumab; D018572:Disease-Free Survival; D004705:Endocytosis / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D053208:Kaplan-Meier Estimate; D008223:Lymphoma / Q000473:pathology / Q000532:radiotherapy*; D020714:Maximum Tolerated Dose; D051379:Mice; D008819:Mice, Nude; D016499:Radioimmunotherapy / Q000379:methods*; D023041:Xenograft Model Antitumor Assays; D015021:Yttrium Radioisotopes / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D015021:Yttrium Radioisotopes; D000077561:Daclizumab