MDA-7/IL-24-based cancer gene therapy: translation from the laboratory to the clinic.
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 tumor-suppressive 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 therapy's clinical utility.
Inoue
Satoshi
S
Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, 77030, USA.
Shanker
Manish
M
Miyahara
Ryo
R
Gopalan
Began
B
Patel
Suraag
S
Oida
Yasuhisa
Y
Branch
Cynthia D
CD
Munshi
Anupama
A
Meyn
Raymond E
RE
Andreeff
Michael
M
Tanaka
Fumihiro
F
Mhashilkar
Abner M
AM
Chada
Sunil
S
Ramesh
Rajagopal
R
D000276:Adjuvants, Immunologic / Q000235:genetics; D002986:Clinical Trials as Topic / Q000639:trends; D003131:Combined Modality Therapy; D004353:Drug Evaluation, Preclinical / Q000639:trends; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000276:immunology; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000235:genetics; D000099180:Interleukin-24
D000276:Adjuvants, Immunologic; D007378:Interleukins; D000099180:Interleukin-24