The efficacy of combined therapy of arsenic trioxide and alpha interferon in human T-cell leukemia virus type-1-infected squirrel monkeys (Saimiri sciureus)

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• 作者：Jean Michel Heraud ; Frank Mortreux ; Fabrice Merien ; Hugues Contamin ; Renaud Mahieux ; Jean Francois Pouliquen ; Eric Wattel ; Antoine Gessain ; Hugues de Thé ; Ali Bazarbachi et al.
• 关键词：Arsenic ; Interferon-alpha ; HTLV-1 ; Squirrel monkeys ; Treatment ; Proviral load ; Flower cells
• 刊名：Antiviral Research
• 出版年：2006
• 出版时间：July 2006
• 年：2006
• 卷：70
• 期：3
• 页码：132-139
• 全文大小：384 K

文摘

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated adult T-cell leukemia/lymphoma (ATLL) has a poor prognosis owing to its intrinsic resistance to chemotherapy. Although zidovudine (AZT) and alpha interferon (IFN-α) give rise to some response and improve the prognosis of ATLL, alternative therapies are needed. Arsenic trioxide (As₂O₃) has been shown to synergize with IFN-α in arresting cell growth and inducing apoptosis of ATLL cells in vitro. In this study, we evaluated the toxicity and the efficacy of this combined treatment in HTLV-1-infected squirrel monkeys (Saimiri sciureus) and HTLV-1 infected cell lines derived therefrom. We first show that treatment with As₂O₃ and IFN-α can induce growth arrest in HTLV-1-transformed monkey T-cell lines in vitro. We then show that treatment of squirrel monkeys with As₂O₃ in vivo is highly toxic at 0.9 or 0.3 mg/day but not at 0.14 mg/day for up to 2 weeks. Although the combination of As₂O₃ and IFN-α did not affect significantly the HTLV-1 proviral load in infected monkeys, it reduced the absolute numbers of CD3⁺, CD4⁺ and CD8⁺ cells during treatment, with a significant reduction in the total number of circulating HTLV-1 flower cells in the infected monkeys with chronic ATLL-like disease.