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Effective therapy of murine models of human leukemia and lymphoma with radiolabeled anti-CD30 antibody, HeFi-1

  1. Author:
    Zhang, M. L.
    Yao, Z. S.
    Patel, H.
    Garmestani, K.
    Zhang, Z.
    Talanov, V. S.
    Plascjak, P. S.
    Goldman, C. K.
    Janik, J. E.
    Brechbiel, M. W.
    Waldmann, T. A.

  2. Author Address

    NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NIH, PET Dept, Clin Ctr, Bethesda, MD 20892 USA. NCI, Lab Anim Sci Program, Ft Detrick, MD 21702 USA. NCI, Appl Dev Res Support Program, Sci Applicat Int Corp, Frederick, MD 21702 USA.;Waldmann, TA, NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.;tawald@helix.nih.gov
    1. Year: 2007
    2. Date: May
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 104
    2. 20
    3. Pages: 8444-8448
  4. Type of Article: Article
  5. ISSN: 0027-8424
  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 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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External Sources

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  2. DOI: 10.1073/pnas.0702496104
  3. View record in Web of Science®
  4. WOS: 000246599900046

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