Melanoma differentiation associated gene-7 (mda-7)/IL-24: A 'magic bullet' for cancer therapy?

Devanand Sarkar; Irina V. Lebedeva; Pankaj Gupta; Luni Emdad; Moira Sauane; Paul Dent; David T. Curiel; Paul B. Fisher

doi:10.1517/14712598.7.5.577

Melanoma differentiation associated gene-7 (mda-7)/IL-24: A 'magic bullet' for cancer therapy?

Devanand Sarkar, Irina V. Lebedeva, Pankaj Gupta, Luni Emdad, Moira Sauane, Paul Dent, David T. Curiel, Paul B. Fisher

Medicine - Veteran's Administration Medical Center

Research output: Contribution to journal › Review article › peer-review

59 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	577-586
Number of pages	10
Journal	Expert opinion on biological therapy
Volume	7
Issue number	5
DOIs	https://doi.org/10.1517/14712598.7.5.577
State	Published - May 2007

Bibliographical note

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.

Keywords

Antiangiogenesis
Antitumor agents
Bipartite adenovirus
Bystander antitumor activity
Cancer-selective apoptosis
Conditional replication-competent adenovirus
ER stress
IL-10 family member
Immune modulation
Radiosensitization
Reactive oxygen species

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Melanoma differentiation associated gene-7 (mda-7)/IL-24: A 'magic bullet' for cancer therapy?",

abstract = "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.",

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note = "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.",

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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.

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Melanoma differentiation associated gene-7 (mda-7)/IL-24: A 'magic bullet' for cancer therapy?

Abstract

Bibliographical note

Keywords

UN SDGs

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