Combination therapy for adult T-cell leukemia-xenografted mice: Flavopiridol and anti-CD25 monoclonal antibody

Meili Zhang, Zhuo Zhang, Carolyn K. Goldman, John Edward Janik, Thomas A. Waldmann

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Adult T-cell leukemia (ATL) develops in a small proportion of individuals infected with human T-cell lymphotrophic virus-1. The leukemia consists of an overabundance of activated T cells, which express CD25 on their cell surfaces. Presently, there is no accepted curative therapy for ATL. Flavopiridol, an inhibitor of cyclin-dependent kinases, has potent antiproliferative effects and antitumor activity. We investigated the therapeutic efficacy of flavopiridol alone and in combination with humanized anti-Tac antibody (HAT), which recognizes CD25, in a murine model of human ATL. The ATL model was established by intraperitoneal injection of MET-1 leukemic cells into nonobese diabetic/severe combined immunodeficient mice. Either flavopiridol, given 2.5 mg/kg body weight daily for 5 days, or HAT, given 100 μg weekly for 4 weeks, inhibited tumor growth as monitored by serum levels of human β-2-microglobulin (β2μ; P < .01), and prolonged survival of the leukemia-bearing mice (P < .05) as compared with the control group. Combination of the 2 agents dramatically enhanced the antitumor effect, as shown by both β2μ levels and survival of the mice, when compared with those in the flavopiridol or HAT alone group (P < .01). The significantly improved therapeutic efficacy by combining flavopiridol with HAT provides support for a clinical trial in the treatment of ATL.

Original languageEnglish (US)
Pages (from-to)1231-1236
Number of pages6
JournalBlood
Volume105
Issue number3
DOIs
StatePublished - Feb 1 2005

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alvocidib
Adult T Cell Leukemia Lymphoma
T-cells
Antibodies, Monoclonal, Humanized
Monoclonal Antibodies
Anti-Idiotypic Antibodies
Antibodies
Leukemia
T-Lymphocytes
Therapeutics
SCID Mice
Cyclin-Dependent Kinases
Bearings (structural)
Intraperitoneal Injections
Body Weight
Clinical Trials
Viruses
Control Groups
Tumors

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Combination therapy for adult T-cell leukemia-xenografted mice : Flavopiridol and anti-CD25 monoclonal antibody. / Zhang, Meili; Zhang, Zhuo; Goldman, Carolyn K.; Janik, John Edward; Waldmann, Thomas A.

In: Blood, Vol. 105, No. 3, 01.02.2005, p. 1231-1236.

Research output: Contribution to journalArticle

Zhang, Meili ; Zhang, Zhuo ; Goldman, Carolyn K. ; Janik, John Edward ; Waldmann, Thomas A. / Combination therapy for adult T-cell leukemia-xenografted mice : Flavopiridol and anti-CD25 monoclonal antibody. In: Blood. 2005 ; Vol. 105, No. 3. pp. 1231-1236.
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abstract = "Adult T-cell leukemia (ATL) develops in a small proportion of individuals infected with human T-cell lymphotrophic virus-1. The leukemia consists of an overabundance of activated T cells, which express CD25 on their cell surfaces. Presently, there is no accepted curative therapy for ATL. Flavopiridol, an inhibitor of cyclin-dependent kinases, has potent antiproliferative effects and antitumor activity. We investigated the therapeutic efficacy of flavopiridol alone and in combination with humanized anti-Tac antibody (HAT), which recognizes CD25, in a murine model of human ATL. The ATL model was established by intraperitoneal injection of MET-1 leukemic cells into nonobese diabetic/severe combined immunodeficient mice. Either flavopiridol, given 2.5 mg/kg body weight daily for 5 days, or HAT, given 100 μg weekly for 4 weeks, inhibited tumor growth as monitored by serum levels of human β-2-microglobulin (β2μ; P < .01), and prolonged survival of the leukemia-bearing mice (P < .05) as compared with the control group. Combination of the 2 agents dramatically enhanced the antitumor effect, as shown by both β2μ levels and survival of the mice, when compared with those in the flavopiridol or HAT alone group (P < .01). The significantly improved therapeutic efficacy by combining flavopiridol with HAT provides support for a clinical trial in the treatment of ATL.",
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