Effective therapy of murine models of human leukemia and lymphoma with radiolabeled anti-CD30 antibody, HeFi-1.
CD30 is a member of the TNF receptor superfamily. Overexpression of CD30 on some neoplasms versus limited expression on normal tissues makes this receptor a promising target for antibody-based therapy. Radioimmunotherapy of cancer with radiolabeled antibodies has shown promise. In this study, we evaluated the therapeutic efficacy of an anti-CD30 antibody, HeFi-1, armed with (211)At in a leukemia (karpas299) model and with (90)Y in a lymphoma (SUDHL-1) model. Furthermore, we investigated the combination therapy of (211)At-HeFi-1 with unmodified HeFi-1 in the leukemia model. Treatment with unmodified HeFi-1 significantly prolonged the survival of the karpas299-bearing mice compared with the controls (P < 0.001). Treatment with (211)At-HeFi-1 showed greater therapeutic efficacy than that with unmodified HeFi-1 as shown by survival of the mice (P < 0.001). Combining these two agents further improved the survival of the mice compared with the groups treated with either (211)At-HeFi-1 (P < 0.05) or unmodified HeFi-1 (P < 0.001) alone. In the lymphoma model, the survival of the SUDHL-1-bearing mice was significantly prolonged by the treatment with (90)Y-HeFi-1 compared with the controls (P < 0.001). In summary, radiolabeled HeFi-1 is very promising for the treatment of CD30-expressing leukemias and lymphomas, and the combination regimen of (211)At-HeFi-1 with unmodified HeFi-1 enhanced the therapeutic efficacy.
Zhang
Meili
M
Metabolism Branch, Center for Cancer Research, National Cancer Institute, PET Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
Yao
Zhengsheng
Z
Patel
Hiral
H
Garmestani
Kayhan
K
Zhang
Zhuo
Z
Talanov
Vladimir S
VS
Plascjak
Paul S
PS
Goldman
Carolyn K
CK
Janik
John E
JE
Brechbiel
Martin W
MW
Waldmann
Thomas A
TA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006801:Humans; D017730:Ki-1 Antigen / Q000276:immunology*; D007938:Leukemia / Q000188:drug therapy* / Q000532:radiotherapy*; D008223:Lymphoma / Q000188:drug therapy* / Q000532:radiotherapy*; D051379:Mice; D008819:Mice, Nude; D016499:Radioimmunotherapy
D000911:Antibodies, Monoclonal; D017730:Ki-1 Antigen