title: Effective therapy of murine models of human leukemia and lymphoma with radiolabeled anti-CD30 antibody, HeFi-1.
abstract: 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.
authors.affiliation: Metabolism Branch, Center for Cancer Research, National Cancer Institute, PET Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Meili
authors.initials: M
authors.lastname: Zhang
authors.forename: Zhengsheng
authors.initials: Z
authors.lastname: Yao
authors.forename: Hiral
authors.initials: H
authors.lastname: Patel
authors.forename: Kayhan
authors.initials: K
authors.lastname: Garmestani
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Talanov
authors.forename: Paul S
authors.initials: PS
authors.lastname: Plascjak
authors.forename: Carolyn K
authors.initials: CK
authors.lastname: Goldman
authors.forename: John E
authors.initials: JE
authors.lastname: Janik
authors.forename: Martin W
authors.initials: MW
authors.lastname: Brechbiel
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Waldmann
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D017730:Ki-1 Antigen