Melanoma differentiation associated gene-7 (mda-7)/IL-24: a 'magic bullet' for cancer therapy?
An ideal cancer gene therapy would selectively kill cancer cells without harming normal cells and induce multipronged 'bystander' antitumor effects, facilitating eradication of both primary and metastatic tumors. Melanoma differentiation associated gene-7 (mda-7)/interleukin-24 (IL-24) exhibits all of these attributes and more. It induces cancer-selective apoptosis, inhibits angiogenesis, stimulates an antitumor immune response, sensitizes cancer cells to radiation and other modalities of conventional therapies, and exhibits profound 'bystander' activity eliminating both primary and distant tumors in animal models. Moreover, a replication-incompetent adenovirus expressing mda-7/IL-24, Ad.mda-7 (INGN-241), has now undergone evaluation in a Phase I clinical trial for multiple solid tumors, including melanomas, and has demonstrated safety and significant objective clinical activity. Considering these exciting observations, mda-7/IL-24 is being hailed as a 'magic bullet' for cancer gene therapy. This review elaborates on the pleiotropic properties of mda-7/IL-24 and unravels novel aspects of the molecule mandating future studies and expanded clinical applications.
Sarkar
Devanand
D
Columbia University Medical Center, Department of Urology, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA. ds2039@columbia.edu
Lebedeva
Irina V
IV
Gupta
Pankaj
P
Emdad
Luni
L
Sauane
Moira
M
Dent
Paul
P
Curiel
David T
DT
Fisher
Paul B
PB
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D024201:Bystander Effect; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D008545:Melanoma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control; D012878:Skin Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome; D000099180:Interleukin-24
D007378:Interleukins; D000099180:Interleukin-24