mda-7/IL-24: Multifunctional cancer-specific apoptosis-inducing cytokine

Pankaj Gupta; Zao zhong Su; Irina V. Lebedeva; Devanand Sarkar; Moira Sauane; Luni Emdad; Michael A. Bachelor; Steven Grant; David T. Curiel; Paul Dent; Paul B. Fisher

doi:10.1016/j.pharmthera.2005.11.005

mda-7/IL-24: Multifunctional cancer-specific apoptosis-inducing cytokine

Pankaj Gupta, Zao zhong Su, Irina V. Lebedeva, Devanand Sarkar, Moira Sauane, Luni Emdad, Michael A. Bachelor, Steven Grant, David T. Curiel, Paul Dent, Paul B. Fisher

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

169 Scopus citations

Abstract

"Differentiation therapy" provides a unique and potentially effective, less toxic treatment paradigm for cancer. Moreover, combining "differentiation therapy" with molecular approaches presents an unparalleled opportunity to identify and clone genes mediating cancer growth control, differentiation, senescence, and programmed cell death (apoptosis). Subtraction hybridization applied to human melanoma cells induced to terminally differentiate by treatment with fibroblast interferon (IFN-β) plus mezerein (MEZ) permitted cloning of melanoma differentiation associated (mda) genes. Founded on its novel properties, one particular mda gene, mda-7, now classified as a member of the interleukin (IL)-10 gene family (IL-24) because of conserved structure, chromosomal location, and cytokine-like properties has become the focus of attention of multiple laboratories. When administered by transfection or adenovirus-transduction into a spectrum of tumor cell types, melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) induces apoptosis, whereas no toxicity is apparent in normal cells. mda-7/IL-24 displays potent "bystander antitumor" activity and also has the capacity to enhance radiation lethality, to induce immune-regulatory activities, and to inhibit tumor angiogenesis. Based on these remarkable attributes and effective antitumor therapy in animal models, this cytokine has taken the important step of entering the clinic. In a Phase I clinical trial, intratumoral injections of adenovirus-administered mda-7/IL-24 (Ad.mda-7) was safe, elicited tumor-regulatory and immune-activating processes, and provided clinically significant activity. This review highlights our current understanding of the diverse activities and properties of this novel cytokine, with potential to become a prominent gene therapy for cancer.

Original language	English (US)
Pages (from-to)	596-628
Number of pages	33
Journal	Pharmacology and Therapeutics
Volume	111
Issue number	3
DOIs	https://doi.org/10.1016/j.pharmthera.2005.11.005
State	Published - Sep 2006
Externally published	Yes

Bibliographical note

Funding Information:
We are indebted to our numerous colleagues who have contributed to our understanding of mda-7/IL-24. The present studies were supported in part by National Institutes of Health grants CA35675, CA097318, CA098712, and P01 CA104177 to PBF; National Institutes of Health grants DK52825, CA88906, CA72955, CA108520, and P01 CA104177 to PD; National Institutes of Health Grant CA083821, CA094084, CA93796, CA111569, and P01 CA104177 to DTC; National Institutes of Health Grant CA63753, CA93738, and CA100866 to SG; Department of Defense grant DAMD17-03-1-0262 to PD; Department of Defense grant DAMD 17-03-1-0209 to SG; Department of Defense grant W81XWH-05-1-0035 to DTC; Department of Defense Army Postdoctoral Fellowships (DS and MS); the Leukemia and Lymphoma Society 6045-03 to SG; the Lustgarten Foundation for Pancreatic Cancer Research (PBF); the Samuel Waxman Cancer Research Foundation (PBF); and the Chernow Endowment (PBF). PBF is the Michael and Stella Chernow Urological Cancer Research Scientist and an SWCRF Investigator. PD is a Universal Leaf Professor in Cell Signaling.

Keywords

Angiogenesis
Antitumor bystander activity
Cell signaling
Differentiation therapy of cancer
Phase I clinical trial
Programmed cell death
Radiosensitization
mda-7/IL-24

UN SDGs

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

Access

10.1016/j.pharmthera.2005.11.005

OpenUrl availability

Full text

Cite this

@article{a2a352900f164076b989812cad0ba0ed,

title = "mda-7/IL-24: Multifunctional cancer-specific apoptosis-inducing cytokine",

abstract = "{"}Differentiation therapy{"} provides a unique and potentially effective, less toxic treatment paradigm for cancer. Moreover, combining {"}differentiation therapy{"} with molecular approaches presents an unparalleled opportunity to identify and clone genes mediating cancer growth control, differentiation, senescence, and programmed cell death (apoptosis). Subtraction hybridization applied to human melanoma cells induced to terminally differentiate by treatment with fibroblast interferon (IFN-β) plus mezerein (MEZ) permitted cloning of melanoma differentiation associated (mda) genes. Founded on its novel properties, one particular mda gene, mda-7, now classified as a member of the interleukin (IL)-10 gene family (IL-24) because of conserved structure, chromosomal location, and cytokine-like properties has become the focus of attention of multiple laboratories. When administered by transfection or adenovirus-transduction into a spectrum of tumor cell types, melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) induces apoptosis, whereas no toxicity is apparent in normal cells. mda-7/IL-24 displays potent {"}bystander antitumor{"} activity and also has the capacity to enhance radiation lethality, to induce immune-regulatory activities, and to inhibit tumor angiogenesis. Based on these remarkable attributes and effective antitumor therapy in animal models, this cytokine has taken the important step of entering the clinic. In a Phase I clinical trial, intratumoral injections of adenovirus-administered mda-7/IL-24 (Ad.mda-7) was safe, elicited tumor-regulatory and immune-activating processes, and provided clinically significant activity. This review highlights our current understanding of the diverse activities and properties of this novel cytokine, with potential to become a prominent gene therapy for cancer.",

keywords = "Angiogenesis, Antitumor bystander activity, Cell signaling, Differentiation therapy of cancer, Phase I clinical trial, Programmed cell death, Radiosensitization, mda-7/IL-24",

author = "Pankaj Gupta and Su, {Zao zhong} and Lebedeva, {Irina V.} and Devanand Sarkar and Moira Sauane and Luni Emdad and Bachelor, {Michael A.} and Steven Grant and Curiel, {David T.} and Paul Dent and Fisher, {Paul B.}",

note = "Funding Information: We are indebted to our numerous colleagues who have contributed to our understanding of mda-7/IL-24. The present studies were supported in part by National Institutes of Health grants CA35675, CA097318, CA098712, and P01 CA104177 to PBF; National Institutes of Health grants DK52825, CA88906, CA72955, CA108520, and P01 CA104177 to PD; National Institutes of Health Grant CA083821, CA094084, CA93796, CA111569, and P01 CA104177 to DTC; National Institutes of Health Grant CA63753, CA93738, and CA100866 to SG; Department of Defense grant DAMD17-03-1-0262 to PD; Department of Defense grant DAMD 17-03-1-0209 to SG; Department of Defense grant W81XWH-05-1-0035 to DTC; Department of Defense Army Postdoctoral Fellowships (DS and MS); the Leukemia and Lymphoma Society 6045-03 to SG; the Lustgarten Foundation for Pancreatic Cancer Research (PBF); the Samuel Waxman Cancer Research Foundation (PBF); and the Chernow Endowment (PBF). PBF is the Michael and Stella Chernow Urological Cancer Research Scientist and an SWCRF Investigator. PD is a Universal Leaf Professor in Cell Signaling.",

year = "2006",

month = sep,

doi = "10.1016/j.pharmthera.2005.11.005",

language = "English (US)",

volume = "111",

pages = "596--628",

journal = "Pharmacology and Therapeutics",

issn = "0163-7258",

number = "3",

}

TY - JOUR

T1 - mda-7/IL-24

T2 - Multifunctional cancer-specific apoptosis-inducing cytokine

AU - Gupta, Pankaj

AU - Su, Zao zhong

AU - Lebedeva, Irina V.

AU - Sarkar, Devanand

AU - Sauane, Moira

AU - Emdad, Luni

AU - Bachelor, Michael A.

AU - Grant, Steven

AU - Curiel, David T.

AU - Dent, Paul

AU - Fisher, Paul B.

N1 - Funding Information: We are indebted to our numerous colleagues who have contributed to our understanding of mda-7/IL-24. The present studies were supported in part by National Institutes of Health grants CA35675, CA097318, CA098712, and P01 CA104177 to PBF; National Institutes of Health grants DK52825, CA88906, CA72955, CA108520, and P01 CA104177 to PD; National Institutes of Health Grant CA083821, CA094084, CA93796, CA111569, and P01 CA104177 to DTC; National Institutes of Health Grant CA63753, CA93738, and CA100866 to SG; Department of Defense grant DAMD17-03-1-0262 to PD; Department of Defense grant DAMD 17-03-1-0209 to SG; Department of Defense grant W81XWH-05-1-0035 to DTC; Department of Defense Army Postdoctoral Fellowships (DS and MS); the Leukemia and Lymphoma Society 6045-03 to SG; the Lustgarten Foundation for Pancreatic Cancer Research (PBF); the Samuel Waxman Cancer Research Foundation (PBF); and the Chernow Endowment (PBF). PBF is the Michael and Stella Chernow Urological Cancer Research Scientist and an SWCRF Investigator. PD is a Universal Leaf Professor in Cell Signaling.

PY - 2006/9

Y1 - 2006/9

N2 - "Differentiation therapy" provides a unique and potentially effective, less toxic treatment paradigm for cancer. Moreover, combining "differentiation therapy" with molecular approaches presents an unparalleled opportunity to identify and clone genes mediating cancer growth control, differentiation, senescence, and programmed cell death (apoptosis). Subtraction hybridization applied to human melanoma cells induced to terminally differentiate by treatment with fibroblast interferon (IFN-β) plus mezerein (MEZ) permitted cloning of melanoma differentiation associated (mda) genes. Founded on its novel properties, one particular mda gene, mda-7, now classified as a member of the interleukin (IL)-10 gene family (IL-24) because of conserved structure, chromosomal location, and cytokine-like properties has become the focus of attention of multiple laboratories. When administered by transfection or adenovirus-transduction into a spectrum of tumor cell types, melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) induces apoptosis, whereas no toxicity is apparent in normal cells. mda-7/IL-24 displays potent "bystander antitumor" activity and also has the capacity to enhance radiation lethality, to induce immune-regulatory activities, and to inhibit tumor angiogenesis. Based on these remarkable attributes and effective antitumor therapy in animal models, this cytokine has taken the important step of entering the clinic. In a Phase I clinical trial, intratumoral injections of adenovirus-administered mda-7/IL-24 (Ad.mda-7) was safe, elicited tumor-regulatory and immune-activating processes, and provided clinically significant activity. This review highlights our current understanding of the diverse activities and properties of this novel cytokine, with potential to become a prominent gene therapy for cancer.

AB - "Differentiation therapy" provides a unique and potentially effective, less toxic treatment paradigm for cancer. Moreover, combining "differentiation therapy" with molecular approaches presents an unparalleled opportunity to identify and clone genes mediating cancer growth control, differentiation, senescence, and programmed cell death (apoptosis). Subtraction hybridization applied to human melanoma cells induced to terminally differentiate by treatment with fibroblast interferon (IFN-β) plus mezerein (MEZ) permitted cloning of melanoma differentiation associated (mda) genes. Founded on its novel properties, one particular mda gene, mda-7, now classified as a member of the interleukin (IL)-10 gene family (IL-24) because of conserved structure, chromosomal location, and cytokine-like properties has become the focus of attention of multiple laboratories. When administered by transfection or adenovirus-transduction into a spectrum of tumor cell types, melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) induces apoptosis, whereas no toxicity is apparent in normal cells. mda-7/IL-24 displays potent "bystander antitumor" activity and also has the capacity to enhance radiation lethality, to induce immune-regulatory activities, and to inhibit tumor angiogenesis. Based on these remarkable attributes and effective antitumor therapy in animal models, this cytokine has taken the important step of entering the clinic. In a Phase I clinical trial, intratumoral injections of adenovirus-administered mda-7/IL-24 (Ad.mda-7) was safe, elicited tumor-regulatory and immune-activating processes, and provided clinically significant activity. This review highlights our current understanding of the diverse activities and properties of this novel cytokine, with potential to become a prominent gene therapy for cancer.

KW - Angiogenesis

KW - Antitumor bystander activity

KW - Cell signaling

KW - Differentiation therapy of cancer

KW - Phase I clinical trial

KW - Programmed cell death

KW - Radiosensitization

KW - mda-7/IL-24

UR - http://www.scopus.com/inward/record.url?scp=33745593993&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745593993&partnerID=8YFLogxK

U2 - 10.1016/j.pharmthera.2005.11.005

DO - 10.1016/j.pharmthera.2005.11.005

M3 - Review article

C2 - 16464504

AN - SCOPUS:33745593993

SN - 0163-7258

VL - 111

SP - 596

EP - 628

JO - Pharmacology and Therapeutics

JF - Pharmacology and Therapeutics

IS - 3

ER -

mda-7/IL-24: Multifunctional cancer-specific apoptosis-inducing cytokine

Abstract

Bibliographical note

Keywords

UN SDGs

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this