期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 20, 页码 8444-8448出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0702496104
关键词
monoclonal antibody; radioimmunotherapy; alpha-emitter; beta-emitter
资金
- Intramural NIH HHS Funding Source: Medline
- NCI NIH HHS [N01-CO-12400, N01CO12400] Funding Source: Medline
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 At-211 in a leukemia (karpas299) model and with Y-90 in a lymphoma (SUDHL-1) model. Furthermore, we investigated the combination therapy of At-211-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 At-211-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 At-211-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 Y-90-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 At-211-HeFi-1 with unmodified HeFi-1 enhanced the therapeutic efficacy.
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