Immunogene therapy using immunomodulating HVJ-E vector augments anti-tumor effects in murine malignant glioma.

Abstract

The hemagglutinating virus of Japan envelope (HVJ-E) vector derived from inactivated replication-defective Sendai virus enhances anti-tumor immunity through activation of effector T cells and natural killer (NK) cells and inhibition of regulatory T cells (Tregs). Interleukin (IL)-2 enhances T cell proliferation and activates T cells and NK cells. However, recent studies have revealed that the application of IL-2 also has immune suppressive effects through expansion of Tregs. Here, we investigated the efficacy of IL-2 gene therapy using immunomodulating HVJ-E vector in murine malignant glioma models. A single intratumoral injection of HVJ-E containing pVAX-mIL-2 significantly suppressed tumor growth of intracranial gliomas, resulting in prolonged survival. Furthermore, HVJ-E, following intracavitary administration, delivered genes into post-operative residual tumor cells. Consequently, prolonged survival resulted from a single intracavitary administration of HVJ-E containing pVAX-mIL-2 following tumor removal. IL-2 gene therapy delivered via the HVJ-E vector significantly inhibited the expansion of Tregs in tumors compared to IL-2 gene transfer using retroviral vector and resulted in marked infiltration of CD4(+) and CD8(+) T cells into tumors. Through inhibition of Treg-mediated immunosuppression, HVJ-E enhanced effector T cell-mediated anti-tumor immunity induced by IL-2. This combination of an immunomodulating vector and immunostimulating cytokine gene shows promise as an attractive, novel immunogene therapy for malignant glioma.

• Authors: Masahide Matsuda, Keisuke Nimura, Takashi Shimbo, Toshimitsu Hamasaki, Tetsuya Yamamoto, Akira Matsumura, Yasufumi Kaneda
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 103 Issue 1 Pg. 19-31 (May 2011) ISSN: 1573-7373 [Electronic] United States
• PMID: 20730616 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Immunologic Factors
• Interleukin-2

Topics

• Animals
• Brain Neoplasms (immunology, therapy)
• Cytokines (metabolism)
• Dendritic Cells (immunology)
• Genetic Therapy
• Genetic Vectors (therapeutic use)
• Glioma (immunology, therapy)
• Immunologic Factors
• Immunotherapy
• Interleukin-2 (genetics)
• Killer Cells, Natural (immunology)
• Lymphocyte Activation
• Mice
• Oncolytic Virotherapy
• Sendai virus (immunology)
• Survival Rate
• T-Lymphocytes (immunology)