Therapeutic and tumor-specific immunity induced by combination of dendritic cells and oncolytic adenovirus expressing IL-12 and 4-1BBL

Jing Hua Huang; Song Nan Zhang; Kyung Ju Choi; Il Kyu Choi; Joo Hang Kim; Mingul Lee; Hoguen Kim; Chae Ok Yun

doi:10.1038/mt.2009.205

Therapeutic and tumor-specific immunity induced by combination of dendritic cells and oncolytic adenovirus expressing IL-12 and 4-1BBL

Jing Hua Huang, Song Nan Zhang, Kyung Ju Choi, Il Kyu Choi, Joo Hang Kim, Mingul Lee, Hoguen Kim, Chae Ok Yun

Department of Dermatology

Research output: Contribution to journal › Article › peer-review

95 Citations (Scopus)

Abstract

Recently, gene-based cytokine treatment has been actively pursued as a new promising approach in treating cancer. In an effort to augment the efficiency of antitumor effect by cytokine-mediated immunotherapy, we selected both interleukin (IL)-12 and 4-1BB ligand (4-1BBL) as suitable cytokines to fully activate the type-1 immune response. Coexpression of IL-12 and 4-1BBL mediated by oncolytic adenovirus (Ad) greatly enhanced the antitumor effect. Further, synergistic enhancement in interferon (IFN)-γ levels were seen in mice treated with oncolytic Ad expressing both IL-12 and 4-1BBL. Next, to improve the overall antitumor immune response, we coadministered IL-12-and 4-1BBL-coexpressing oncolytic Ad with dendritic cells (DCs). Combination treatment of IL-12-and 4-1BBL-coexpressing oncolytic Ad and DCs elicited greater antitumor and antimetastatic effects than either treatment alone. Moreover, enhanced type-1 antitumor immune response and higher migratory abilities of DCs in tumors were also observed in the combination arms. The nature of the enhanced antitumor immune response seems to be mediated through the enhanced cytolytic activity of cytotoxic T lymphocytes (CTLs) and IFN-γ-releasing immune cells. Taken together, these data highlight the potential therapeutic benefit of combining IL-12-and 4-1BBL-coexpressing oncolytic Ad with DCs and warrants further evaluation in the clinic.

Original language	English
Pages (from-to)	264-274
Number of pages	11
Journal	Molecular Therapy
Volume	18
Issue number	2
DOIs	https://doi.org/10.1038/mt.2009.205
Publication status	Published - 2010 Feb

Bibliographical note

Funding Information:
This work was supported by grants from the Ministry of Commerce Industry and Energy (10030051, C.-O.Y.), the Korea Science and engineering foundation (R04-2004-000-10011-0, R01-2006-000-10084-0, R15-2004-024-02001-0, M10416130002-04N1613-00210, C.-O.Y.), and through its Nuclear Research & Development Program (2007-00299, C.-O.Y.) of the Korea Science and Engineering Foundation. J.-H.H., S.-N.Z., and K.-J.C are graduate students sponsored by the Brain Korea 21 Project for Medical Science, and I.-K.C is a graduate student sponsored by the Graduate Program for Nanomedical Science, Yonsei University College of Medicine, Seoul, South Korea.

All Science Journal Classification (ASJC) codes

Molecular Medicine
Molecular Biology
Genetics
Pharmacology
Drug Discovery

UN SDGs

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

Access to Document

10.1038/mt.2009.205

Cite this

@article{5192e15df8ed47b4ab3ad3e8d5d8a430,

title = "Therapeutic and tumor-specific immunity induced by combination of dendritic cells and oncolytic adenovirus expressing IL-12 and 4-1BBL",

abstract = "Recently, gene-based cytokine treatment has been actively pursued as a new promising approach in treating cancer. In an effort to augment the efficiency of antitumor effect by cytokine-mediated immunotherapy, we selected both interleukin (IL)-12 and 4-1BB ligand (4-1BBL) as suitable cytokines to fully activate the type-1 immune response. Coexpression of IL-12 and 4-1BBL mediated by oncolytic adenovirus (Ad) greatly enhanced the antitumor effect. Further, synergistic enhancement in interferon (IFN)-γ levels were seen in mice treated with oncolytic Ad expressing both IL-12 and 4-1BBL. Next, to improve the overall antitumor immune response, we coadministered IL-12-and 4-1BBL-coexpressing oncolytic Ad with dendritic cells (DCs). Combination treatment of IL-12-and 4-1BBL-coexpressing oncolytic Ad and DCs elicited greater antitumor and antimetastatic effects than either treatment alone. Moreover, enhanced type-1 antitumor immune response and higher migratory abilities of DCs in tumors were also observed in the combination arms. The nature of the enhanced antitumor immune response seems to be mediated through the enhanced cytolytic activity of cytotoxic T lymphocytes (CTLs) and IFN-γ-releasing immune cells. Taken together, these data highlight the potential therapeutic benefit of combining IL-12-and 4-1BBL-coexpressing oncolytic Ad with DCs and warrants further evaluation in the clinic.",

author = "Huang, {Jing Hua} and Zhang, {Song Nan} and Choi, {Kyung Ju} and Choi, {Il Kyu} and Kim, {Joo Hang} and Mingul Lee and Hoguen Kim and Yun, {Chae Ok}",

note = "Funding Information: This work was supported by grants from the Ministry of Commerce Industry and Energy (10030051, C.-O.Y.), the Korea Science and engineering foundation (R04-2004-000-10011-0, R01-2006-000-10084-0, R15-2004-024-02001-0, M10416130002-04N1613-00210, C.-O.Y.), and through its Nuclear Research & Development Program (2007-00299, C.-O.Y.) of the Korea Science and Engineering Foundation. J.-H.H., S.-N.Z., and K.-J.C are graduate students sponsored by the Brain Korea 21 Project for Medical Science, and I.-K.C is a graduate student sponsored by the Graduate Program for Nanomedical Science, Yonsei University College of Medicine, Seoul, South Korea.",

year = "2010",

month = feb,

doi = "10.1038/mt.2009.205",

language = "English",

volume = "18",

pages = "264--274",

journal = "Molecular Therapy",

issn = "1525-0016",

publisher = "Nature Publishing Group",

number = "2",

}

TY - JOUR

T1 - Therapeutic and tumor-specific immunity induced by combination of dendritic cells and oncolytic adenovirus expressing IL-12 and 4-1BBL

AU - Huang, Jing Hua

AU - Zhang, Song Nan

AU - Choi, Kyung Ju

AU - Choi, Il Kyu

AU - Kim, Joo Hang

AU - Lee, Mingul

AU - Kim, Hoguen

AU - Yun, Chae Ok

N1 - Funding Information: This work was supported by grants from the Ministry of Commerce Industry and Energy (10030051, C.-O.Y.), the Korea Science and engineering foundation (R04-2004-000-10011-0, R01-2006-000-10084-0, R15-2004-024-02001-0, M10416130002-04N1613-00210, C.-O.Y.), and through its Nuclear Research & Development Program (2007-00299, C.-O.Y.) of the Korea Science and Engineering Foundation. J.-H.H., S.-N.Z., and K.-J.C are graduate students sponsored by the Brain Korea 21 Project for Medical Science, and I.-K.C is a graduate student sponsored by the Graduate Program for Nanomedical Science, Yonsei University College of Medicine, Seoul, South Korea.

PY - 2010/2

Y1 - 2010/2

N2 - Recently, gene-based cytokine treatment has been actively pursued as a new promising approach in treating cancer. In an effort to augment the efficiency of antitumor effect by cytokine-mediated immunotherapy, we selected both interleukin (IL)-12 and 4-1BB ligand (4-1BBL) as suitable cytokines to fully activate the type-1 immune response. Coexpression of IL-12 and 4-1BBL mediated by oncolytic adenovirus (Ad) greatly enhanced the antitumor effect. Further, synergistic enhancement in interferon (IFN)-γ levels were seen in mice treated with oncolytic Ad expressing both IL-12 and 4-1BBL. Next, to improve the overall antitumor immune response, we coadministered IL-12-and 4-1BBL-coexpressing oncolytic Ad with dendritic cells (DCs). Combination treatment of IL-12-and 4-1BBL-coexpressing oncolytic Ad and DCs elicited greater antitumor and antimetastatic effects than either treatment alone. Moreover, enhanced type-1 antitumor immune response and higher migratory abilities of DCs in tumors were also observed in the combination arms. The nature of the enhanced antitumor immune response seems to be mediated through the enhanced cytolytic activity of cytotoxic T lymphocytes (CTLs) and IFN-γ-releasing immune cells. Taken together, these data highlight the potential therapeutic benefit of combining IL-12-and 4-1BBL-coexpressing oncolytic Ad with DCs and warrants further evaluation in the clinic.

AB - Recently, gene-based cytokine treatment has been actively pursued as a new promising approach in treating cancer. In an effort to augment the efficiency of antitumor effect by cytokine-mediated immunotherapy, we selected both interleukin (IL)-12 and 4-1BB ligand (4-1BBL) as suitable cytokines to fully activate the type-1 immune response. Coexpression of IL-12 and 4-1BBL mediated by oncolytic adenovirus (Ad) greatly enhanced the antitumor effect. Further, synergistic enhancement in interferon (IFN)-γ levels were seen in mice treated with oncolytic Ad expressing both IL-12 and 4-1BBL. Next, to improve the overall antitumor immune response, we coadministered IL-12-and 4-1BBL-coexpressing oncolytic Ad with dendritic cells (DCs). Combination treatment of IL-12-and 4-1BBL-coexpressing oncolytic Ad and DCs elicited greater antitumor and antimetastatic effects than either treatment alone. Moreover, enhanced type-1 antitumor immune response and higher migratory abilities of DCs in tumors were also observed in the combination arms. The nature of the enhanced antitumor immune response seems to be mediated through the enhanced cytolytic activity of cytotoxic T lymphocytes (CTLs) and IFN-γ-releasing immune cells. Taken together, these data highlight the potential therapeutic benefit of combining IL-12-and 4-1BBL-coexpressing oncolytic Ad with DCs and warrants further evaluation in the clinic.

UR - http://www.scopus.com/inward/record.url?scp=76349109690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=76349109690&partnerID=8YFLogxK

U2 - 10.1038/mt.2009.205

DO - 10.1038/mt.2009.205

M3 - Article

C2 - 19738604

AN - SCOPUS:76349109690

SN - 1525-0016

VL - 18

SP - 264

EP - 274

JO - Molecular Therapy

JF - Molecular Therapy

IS - 2

ER -

Therapeutic and tumor-specific immunity induced by combination of dendritic cells and oncolytic adenovirus expressing IL-12 and 4-1BBL

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this