Retroviral transfer of CPP32β gene into malignant gliomas in vitro and in vivo

• Published in: Cancer research (Chicago, Ill.) Ill.), 1998-03, Vol.58 (5), p.962-967
• Main Authors: KONDO, s, TANAKA, Y, KONDO, Y, ISHIZAKA, Y, HITOMI, M, HAQQI, T, JINBO LIU, BARNETT, G. H, ALNEMRI, E. S, BARNA, B. P
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biotechnology; Fundamental and applied biological sciences. Psychology; Gene therapy; Health. Pharmaceutical industry; Industrial applications and implications. Economical aspects
• ISSN: 0008-5472; 1538-7445

Malignant gliomas are highly aggressive neoplasms that are very resistant to current therapeutic approaches, including irradiation, chemotherapy, and immunotherapy. To improve the prognosis, it is absolutely essential to explore novel modalities of treatment. Recently, we have demonstrated that interleukin 1 beta -converting enzyme (ICE), a mammalian homologue of the Caenorhabditis elegans cell death gene ced-3, induces apoptotic cell death in malignant glioma cells. To date, ICE and ICE-like proteases (the ICE family), such as Ich-1 sub(L), CPP32 beta , Mch2 alpha , and Mch3 alpha , have been shown to mediate apoptosis in some cells. The purpose of this study is to determine whether the ICE gene family functions as a useful tool for the treatment of malignant glioma cells through induction of apoptosis. The transient transfection assays showed that CPP32 beta and Mch2 alpha genes induced apoptotic cell death in malignant glioma cells more effectively than did the ICE, Ich-1 sub(L), and Mch3 alpha genes. To improve the efficiency of gene transfer into malignant glioma cells, we constructed the retroviral vectors containing the ICE gene family. The retroviral transfer of CPP32 beta or Mch2 alpha gene effectively induced apoptosis in malignant glioma cells in vitro. Furthermore, treatment of tumors grown in mice with retrovirus containing CPP32 beta significantly inhibited growth of the tumors through induction of apoptosis. The retroviral transfer of CPP32 beta or Mch2 alpha , therefore, may be a novel and promising approach for the treatment of malignant glioma, an invariably fatal tumor.