Effective Therapy of Murine Models of Human Leukemia and Lymphoma with Radiolabeled Anti-CD30 Antibody, HeFi-1

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2007 May 10

PMID 17488826

Citations 11

Authors

Meili Zhang

Zhengsheng Yao

Hiral Patel

Kayhan Garmestani

Zhuo Zhang

Vladimir S Talanov

Paul S Plascjak

Carolyn K Goldman

John E Janik

Martin W Brechbiel

Thomas A Waldmann

Affiliations

Soon will be listed here.

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.

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