TY - JOUR
T1 - Melanoma differentiation associated gene-7 (mda-7)/IL-24
T2 - A 'magic bullet' for cancer therapy?
AU - Sarkar, Devanand
AU - Lebedeva, Irina V.
AU - Gupta, Pankaj
AU - Emdad, Luni
AU - Sauane, Moira
AU - Dent, Paul
AU - Curiel, David T.
AU - Fisher, Paul B.
N1 - Funding Information:
The present studies were supported in part by NIH grants R01 CA35675, R01 CA97318, R01 CA98712 and P01 CA104177, Army DOD grant DAMD17-03-1-0290, the Lustgarten Foundation for Pancreatic Cancer Research, the Samuel Cancer Research Foundation and the Chernow Endowment. The author is the Michael and Stella Chernow Urological Cancer Research Scientist and a SWCRF Investigator.
PY - 2007/5
Y1 - 2007/5
N2 - 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.
AB - 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.
KW - Antiangiogenesis
KW - Antitumor agents
KW - Bipartite adenovirus
KW - Bystander antitumor activity
KW - Cancer-selective apoptosis
KW - Conditional replication-competent adenovirus
KW - ER stress
KW - IL-10 family member
KW - Immune modulation
KW - Radiosensitization
KW - Reactive oxygen species
UR - http://www.scopus.com/inward/record.url?scp=34248156775&partnerID=8YFLogxK
U2 - 10.1517/14712598.7.5.577
DO - 10.1517/14712598.7.5.577
M3 - Review article
C2 - 17477796
AN - SCOPUS:34248156775
SN - 1471-2598
VL - 7
SP - 577
EP - 586
JO - Expert opinion on biological therapy
JF - Expert opinion on biological therapy
IS - 5
ER -