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

Meili Zhang, Zhengsheng Yao, Hiral Patel, Kayhan Garmestani, Zhuo Zhang, Vladimir S. Talanov, Paul S. Plascjak, Carolyn K. Goldman, John Edward Janik, Martin W. Brechbiel, Thomas A. Waldmann

Research output: Contribution to journalArticle

20 Citations (Scopus)

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 211At in a leukemia (karpas299) model and with 90Y in a lymphoma (SUDHL-1) model. Furthermore, we investigated the combination therapy of 211At-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 211At-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 211At-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 90Y-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 211At-HeFi-1 with unmodified HeFi-1 enhanced the therapeutic efficacy.

Original languageEnglish (US)
Pages (from-to)8444-8448
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number20
DOIs
StatePublished - May 15 2007

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Anti-Idiotypic Antibodies
Lymphoma
Leukemia
Therapeutics
Radioimmunotherapy
Survival
Antibodies
Tumor Necrosis Factor Receptors
Neoplasms

Keywords

  • Monoclonal antibody
  • Radioimmunotherapy
  • α-emitter
  • β-emitter

ASJC Scopus subject areas

  • General

Cite this

Effective therapy of murine models of human leukemia and lymphoma with radiolabeled anti-CD30 antibody, HeFi-1. / Zhang, Meili; Yao, Zhengsheng; Patel, Hiral; Garmestani, Kayhan; Zhang, Zhuo; Talanov, Vladimir S.; Plascjak, Paul S.; Goldman, Carolyn K.; Janik, John Edward; Brechbiel, Martin W.; Waldmann, Thomas A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 20, 15.05.2007, p. 8444-8448.

Research output: Contribution to journalArticle

Zhang, M, Yao, Z, Patel, H, Garmestani, K, Zhang, Z, Talanov, VS, Plascjak, PS, Goldman, CK, Janik, JE, Brechbiel, MW & Waldmann, TA 2007, 'Effective therapy of murine models of human leukemia and lymphoma with radiolabeled anti-CD30 antibody, HeFi-1', Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 20, pp. 8444-8448. https://doi.org/10.1073/pnas.0702496104
Zhang, Meili ; Yao, Zhengsheng ; Patel, Hiral ; Garmestani, Kayhan ; Zhang, Zhuo ; Talanov, Vladimir S. ; Plascjak, Paul S. ; Goldman, Carolyn K. ; Janik, John Edward ; Brechbiel, Martin W. ; Waldmann, Thomas A. / Effective therapy of murine models of human leukemia and lymphoma with radiolabeled anti-CD30 antibody, HeFi-1. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 20. pp. 8444-8448.
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T1 - Effective therapy of murine models of human leukemia and lymphoma with radiolabeled anti-CD30 antibody, HeFi-1

AU - Zhang, Meili

AU - Yao, Zhengsheng

AU - Patel, Hiral

AU - Garmestani, Kayhan

AU - Zhang, Zhuo

AU - Talanov, Vladimir S.

AU - Plascjak, Paul S.

AU - Goldman, Carolyn K.

AU - Janik, John Edward

AU - Brechbiel, Martin W.

AU - Waldmann, Thomas A.

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N2 - 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 211At in a leukemia (karpas299) model and with 90Y in a lymphoma (SUDHL-1) model. Furthermore, we investigated the combination therapy of 211At-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 211At-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 211At-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 90Y-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 211At-HeFi-1 with unmodified HeFi-1 enhanced the therapeutic efficacy.

AB - 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 211At in a leukemia (karpas299) model and with 90Y in a lymphoma (SUDHL-1) model. Furthermore, we investigated the combination therapy of 211At-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 211At-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 211At-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 90Y-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 211At-HeFi-1 with unmodified HeFi-1 enhanced the therapeutic efficacy.

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