Abstract
Despite recent advances in treatment strategies, the overall 5-year survival rate for patients with common epithelial cancers is poor largely because of the difficulty in treating metastatic cancers. Therefore, therapeutic agents are urgently needed that can effectively inhibit both primary epithelial tumors and their metastases. One such agent that has shown promise in preclinical studies is the tumor suppressor/cytokine, melanoma differentiation associated gene-7 also known as interleukin-24 (mda-7/IL-24). Preclinical studies from our and other laboratories have shown that overexpression of MDA-7/IL-24 causes a strong tumor- suppressive effect in many human cancer cells but spares normal cells. This gene therapy also enhances the tumorsuppressive activity of radiotherapy and chemotherapy. Secreted MDA-7 protein that is glycosylated also has been shown to have potent antiangiogenic activity both in vitro and in vivo. Studies examining the immune properties of mda-7 have shown that MDA-7/IL-24 unlike the related IL-10, functions as a Th1 cytokine. Recently, an MDA-7 protein-mediated "bystander effect" on tumor cells has been documented. Building on these findings we successfully completed a Phase I clinical trial of adenovirus-based mda-7 cancer therapy that confirmed the safety of this gene therapy. Phase II trials evaluating the efficacy of mda-7-based gene therapy are warranted. The outcome of such ongoing mda-7-based gene therapy trials will allow us to better understand this therapys clinical utility.
Keywords: Cancer, cytokine, immunity, IL-10, receptor, apoptosis, angiogenesis, chemotherapy, radiation
Current Gene Therapy
Title: MDA-7/IL-24-Based Cancer Gene Therapy: Translation from the Laboratory to the Clinic
Volume: 6 Issue: 1
Author(s): Satoshi Inoue, Manish Shanker, Ryo Miyahara, Began Gopalan, Suraag Patel, Yasuhisa Oida, Cynthia D. Branch, Anupama Munshi, Raymond E. Meyn, Michael Andreeff, Fumihiro Tanaka, Abner M. Mhashilkar, Sunil Chada and Rajagopal Ramesh
Affiliation:
Keywords: Cancer, cytokine, immunity, IL-10, receptor, apoptosis, angiogenesis, chemotherapy, radiation
Abstract: Despite recent advances in treatment strategies, the overall 5-year survival rate for patients with common epithelial cancers is poor largely because of the difficulty in treating metastatic cancers. Therefore, therapeutic agents are urgently needed that can effectively inhibit both primary epithelial tumors and their metastases. One such agent that has shown promise in preclinical studies is the tumor suppressor/cytokine, melanoma differentiation associated gene-7 also known as interleukin-24 (mda-7/IL-24). Preclinical studies from our and other laboratories have shown that overexpression of MDA-7/IL-24 causes a strong tumor- suppressive effect in many human cancer cells but spares normal cells. This gene therapy also enhances the tumorsuppressive activity of radiotherapy and chemotherapy. Secreted MDA-7 protein that is glycosylated also has been shown to have potent antiangiogenic activity both in vitro and in vivo. Studies examining the immune properties of mda-7 have shown that MDA-7/IL-24 unlike the related IL-10, functions as a Th1 cytokine. Recently, an MDA-7 protein-mediated "bystander effect" on tumor cells has been documented. Building on these findings we successfully completed a Phase I clinical trial of adenovirus-based mda-7 cancer therapy that confirmed the safety of this gene therapy. Phase II trials evaluating the efficacy of mda-7-based gene therapy are warranted. The outcome of such ongoing mda-7-based gene therapy trials will allow us to better understand this therapys clinical utility.
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Inoue Satoshi, Shanker Manish, Miyahara Ryo, Gopalan Began, Patel Suraag, Oida Yasuhisa, Branch D. Cynthia, Munshi Anupama, Meyn E. Raymond, Andreeff Michael, Tanaka Fumihiro, Mhashilkar M. Abner, Chada Sunil and Ramesh Rajagopal, MDA-7/IL-24-Based Cancer Gene Therapy: Translation from the Laboratory to the Clinic, Current Gene Therapy 2006; 6 (1) . https://dx.doi.org/10.2174/156652306775515574
DOI https://dx.doi.org/10.2174/156652306775515574 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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