Vaccination with dendritic cells transfected with BAK and BAX siRNA enhances antigen-specific immune responses by prolonging dendritic cell life

Shiwen Peng, Tae Woo Kim, Jin Hyup Lee, M. U. Yang, H. E. Liangmei, Chien Fu Hung, T. C. Wu

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Dendritic cell-based vaccines have become an important approach for the treatment of malignancies. Numerous techniques have recently been designed to optimize dendritic cell activation, tumor antigen delivery to dendritic cells, and induction of tumor-specific immune responses in vivo. Dendritic cells (DCs), however, have a limited life span because they are subject to apoptotic cell death mediated by T cells, hindering their long-term ability to prime antigen-specific T cells. Small interfering RNA targeting Bak and Bax antiapoptotic proteins can be used to allow transfected DCs to resist killing by T cells in vivo. In this study, we show that human papillomavirus E7-loaded dendritic cells transfected with BAK/BAX siRNA downregulate Bak and Bax protein expression and become resistant to killing by T cells, leading to enhanced E7-specific CD8 + T cell activation and antitumor effects in vivo. More importantly, we found that vaccination with E7-loaded DCs transfected with BAK/BAX siRNA was capable of generating a strong therapeutic effect in vaccinated mice, compared with DCs transfected with control siRNA. Our data indicate that transfection of dendritic cells with BAK/BAX siRNA represents a plausible strategy for enhancing dendritic cell-based vaccine potency.

Original languageEnglish
Pages (from-to)584-593
Number of pages10
JournalHuman Gene Therapy
Volume16
Issue number5
DOIs
Publication statusPublished - 2005 May 1
Externally publishedYes

Fingerprint

Histocompatibility Antigens Class II
Dendritic Cells
Small Interfering RNA
Vaccination
T-Lymphocytes
bcl-2-Associated X Protein
bcl-2 Homologous Antagonist-Killer Protein
Vaccine Potency
Neoplasm Antigens
Therapeutic Uses
Transfection
Neoplasms
Cell Death
Down-Regulation
Vaccines
Antigens

ASJC Scopus subject areas

  • Genetics

Cite this

Vaccination with dendritic cells transfected with BAK and BAX siRNA enhances antigen-specific immune responses by prolonging dendritic cell life. / Peng, Shiwen; Kim, Tae Woo; Lee, Jin Hyup; Yang, M. U.; Liangmei, H. E.; Hung, Chien Fu; Wu, T. C.

In: Human Gene Therapy, Vol. 16, No. 5, 01.05.2005, p. 584-593.

Research output: Contribution to journalArticle

Peng, Shiwen ; Kim, Tae Woo ; Lee, Jin Hyup ; Yang, M. U. ; Liangmei, H. E. ; Hung, Chien Fu ; Wu, T. C. / Vaccination with dendritic cells transfected with BAK and BAX siRNA enhances antigen-specific immune responses by prolonging dendritic cell life. In: Human Gene Therapy. 2005 ; Vol. 16, No. 5. pp. 584-593.
@article{77d500fa8b4147c6b3e2072c709865fd,
title = "Vaccination with dendritic cells transfected with BAK and BAX siRNA enhances antigen-specific immune responses by prolonging dendritic cell life",
abstract = "Dendritic cell-based vaccines have become an important approach for the treatment of malignancies. Numerous techniques have recently been designed to optimize dendritic cell activation, tumor antigen delivery to dendritic cells, and induction of tumor-specific immune responses in vivo. Dendritic cells (DCs), however, have a limited life span because they are subject to apoptotic cell death mediated by T cells, hindering their long-term ability to prime antigen-specific T cells. Small interfering RNA targeting Bak and Bax antiapoptotic proteins can be used to allow transfected DCs to resist killing by T cells in vivo. In this study, we show that human papillomavirus E7-loaded dendritic cells transfected with BAK/BAX siRNA downregulate Bak and Bax protein expression and become resistant to killing by T cells, leading to enhanced E7-specific CD8 + T cell activation and antitumor effects in vivo. More importantly, we found that vaccination with E7-loaded DCs transfected with BAK/BAX siRNA was capable of generating a strong therapeutic effect in vaccinated mice, compared with DCs transfected with control siRNA. Our data indicate that transfection of dendritic cells with BAK/BAX siRNA represents a plausible strategy for enhancing dendritic cell-based vaccine potency.",
author = "Shiwen Peng and Kim, {Tae Woo} and Lee, {Jin Hyup} and Yang, {M. U.} and Liangmei, {H. E.} and Hung, {Chien Fu} and Wu, {T. C.}",
year = "2005",
month = "5",
day = "1",
doi = "10.1089/hum.2005.16.584",
language = "English",
volume = "16",
pages = "584--593",
journal = "Human Gene Therapy",
issn = "1043-0342",
publisher = "Mary Ann Liebert Inc.",
number = "5",

}

TY - JOUR

T1 - Vaccination with dendritic cells transfected with BAK and BAX siRNA enhances antigen-specific immune responses by prolonging dendritic cell life

AU - Peng, Shiwen

AU - Kim, Tae Woo

AU - Lee, Jin Hyup

AU - Yang, M. U.

AU - Liangmei, H. E.

AU - Hung, Chien Fu

AU - Wu, T. C.

PY - 2005/5/1

Y1 - 2005/5/1

N2 - Dendritic cell-based vaccines have become an important approach for the treatment of malignancies. Numerous techniques have recently been designed to optimize dendritic cell activation, tumor antigen delivery to dendritic cells, and induction of tumor-specific immune responses in vivo. Dendritic cells (DCs), however, have a limited life span because they are subject to apoptotic cell death mediated by T cells, hindering their long-term ability to prime antigen-specific T cells. Small interfering RNA targeting Bak and Bax antiapoptotic proteins can be used to allow transfected DCs to resist killing by T cells in vivo. In this study, we show that human papillomavirus E7-loaded dendritic cells transfected with BAK/BAX siRNA downregulate Bak and Bax protein expression and become resistant to killing by T cells, leading to enhanced E7-specific CD8 + T cell activation and antitumor effects in vivo. More importantly, we found that vaccination with E7-loaded DCs transfected with BAK/BAX siRNA was capable of generating a strong therapeutic effect in vaccinated mice, compared with DCs transfected with control siRNA. Our data indicate that transfection of dendritic cells with BAK/BAX siRNA represents a plausible strategy for enhancing dendritic cell-based vaccine potency.

AB - Dendritic cell-based vaccines have become an important approach for the treatment of malignancies. Numerous techniques have recently been designed to optimize dendritic cell activation, tumor antigen delivery to dendritic cells, and induction of tumor-specific immune responses in vivo. Dendritic cells (DCs), however, have a limited life span because they are subject to apoptotic cell death mediated by T cells, hindering their long-term ability to prime antigen-specific T cells. Small interfering RNA targeting Bak and Bax antiapoptotic proteins can be used to allow transfected DCs to resist killing by T cells in vivo. In this study, we show that human papillomavirus E7-loaded dendritic cells transfected with BAK/BAX siRNA downregulate Bak and Bax protein expression and become resistant to killing by T cells, leading to enhanced E7-specific CD8 + T cell activation and antitumor effects in vivo. More importantly, we found that vaccination with E7-loaded DCs transfected with BAK/BAX siRNA was capable of generating a strong therapeutic effect in vaccinated mice, compared with DCs transfected with control siRNA. Our data indicate that transfection of dendritic cells with BAK/BAX siRNA represents a plausible strategy for enhancing dendritic cell-based vaccine potency.

UR - http://www.scopus.com/inward/record.url?scp=19644396618&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=19644396618&partnerID=8YFLogxK

U2 - 10.1089/hum.2005.16.584

DO - 10.1089/hum.2005.16.584

M3 - Article

VL - 16

SP - 584

EP - 593

JO - Human Gene Therapy

JF - Human Gene Therapy

SN - 1043-0342

IS - 5

ER -