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

doi:10.1073/pnas.0702496104

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

Pulmonary Disease

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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 language	English (US)
Pages (from-to)	8444-8448
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	104
Issue number	20
DOIs	https://doi.org/10.1073/pnas.0702496104
State	Published - May 15 2007

Keywords

Monoclonal antibody
Radioimmunotherapy
α-emitter
β-emitter

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Zhang, M., Yao, Z., Patel, H., Garmestani, K., Zhang, Z., Talanov, V. S., Plascjak, P. S., Goldman, C. K., Janik, J. E., Brechbiel, M. W., & Waldmann, T. A. (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, 104(20), 8444-8448. https://doi.org/10.1073/pnas.0702496104

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

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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 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.",

keywords = "Monoclonal antibody, Radioimmunotherapy, α-emitter, β-emitter",

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

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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.

PY - 2007/5/15

Y1 - 2007/5/15

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.

KW - Monoclonal antibody

KW - Radioimmunotherapy

KW - α-emitter

KW - β-emitter

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SN - 0027-8424

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EP - 8448

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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