Markedly additive antitumor activity with the combination of a selective survivin suppressant YM155 and alemtuzumab in adult T-cell leukemia

Jing Chen, Cynthia A. Pise-Masison, Joanna H. Shih, John C. Morris, John Edward Janik, Kevin C. Conlon, Anne Keating, Thomas A. Waldmann

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29 Scopus citations

Abstract

Adult T-cell leukemia (ATL) is an aggressive malignancy of CD4+CD25+ lymphocytes caused by human T-cell lymphotropic virus type 1. Currently, there is no accepted curative therapy for ATL. In gene expression profiling, the antiapoptotic protein survivin (BIRC5) demonstrated a striking increase in ATL, and its expression was increased in patient ATL cells resistant to the anti-CD52 monoclonal antibody alemtuzumab (Campath-1H). In this study, we investigated the antitumor activity of a small-molecule survivin suppressant YM155 alone and in combination with alemtuzumab in a murine model of human ATL (MET-1). Both YM155 alone and its combination with alemtuzumab demonstrated therapeutic efficacy by lowering serum soluble IL-2Rα (sIL-2Rα) levels (P < .001) and prolonged the survival of tumor-bearing mice (P < .0001). Moreover, the combination of YM155 with alemtuzumab demonstrated markedly additive antitumor activity by significantly lowering serum sIL-2Rα levels and improving the survival of leukemia-bearing mice compared with monotherapy with either YM155 (P < .001) or alemtuzumab (P < .05). More significantly, all mice that received the combination therapy survived and were tumor free >6 months after treatment. Our data support a clinical trial of the combination of YM155 with alemtuzumab in ATL.

Original languageEnglish (US)
Pages (from-to)2029-2037
Number of pages9
JournalBlood
Volume121
Issue number11
DOIs
Publication statusPublished - Jan 1 2013

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Chen, J., Pise-Masison, C. A., Shih, J. H., Morris, J. C., Janik, J. E., Conlon, K. C., ... Waldmann, T. A. (2013). Markedly additive antitumor activity with the combination of a selective survivin suppressant YM155 and alemtuzumab in adult T-cell leukemia. Blood, 121(11), 2029-2037. https://doi.org/10.1182/blood-2012-05-427773