PMID- 15916483
OWN - NLM
STAT- MEDLINE
DCOM- 20050808
LR  - 20220310
IS  - 1043-0342 (Print)
IS  - 1557-7422 (Electronic)
IS  - 1043-0342 (Linking)
VI  - 16
IP  - 5
DP  - 2005 May
TI  - Vaccination with dendritic cells transfected with BAK and BAX siRNA enhances 
      antigen-specific immune responses by prolonging dendritic cell life.
PG  - 584-93
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.
FAU - Peng, Shiwen
AU  - Peng S
AD  - Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland 
      21205, USA.
FAU - Kim, Tae Woo
AU  - Kim TW
FAU - Lee, Jin Hyup
AU  - Lee JH
FAU - Yang, Mu
AU  - Yang M
FAU - He, Liangmei
AU  - He L
FAU - Hung, Chien-Fu
AU  - Hung CF
FAU - Wu, T-C
AU  - Wu TC
LA  - eng
GR  - P50 CA098252/CA/NCI NIH HHS/United States
GR  - R01 CA114425/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (BAK1 protein, human)
RN  - 0 (BAX protein, human)
RN  - 0 (Bak1 protein, mouse)
RN  - 0 (Bax protein, mouse)
RN  - 0 (Membrane Proteins)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (Peptides)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Viral Vaccines)
RN  - 0 (bcl-2 Homologous Antagonist-Killer Protein)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Cell Line, Tumor
MH  - Dendritic Cells/*immunology
MH  - Down-Regulation
MH  - Gene Expression Regulation/immunology
MH  - Humans
MH  - Lymphocyte Activation
MH  - Membrane Proteins/genetics/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oncogene Proteins, Viral/chemistry/immunology
MH  - Papillomavirus E7 Proteins
MH  - Peptides/pharmacology
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/*immunology
MH  - RNA, Small Interfering/*metabolism
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Transfection
MH  - *Vaccination
MH  - Viral Vaccines/immunology
MH  - bcl-2 Homologous Antagonist-Killer Protein
MH  - bcl-2-Associated X Protein
PMC - PMC3181105
MID - NIHMS324711
EDAT- 2005/05/27 09:00
MHDA- 2005/08/09 09:00
PMCR- 2011/09/27
CRDT- 2005/05/27 09:00
PHST- 2005/05/27 09:00 [pubmed]
PHST- 2005/08/09 09:00 [medline]
PHST- 2005/05/27 09:00 [entrez]
PHST- 2011/09/27 00:00 [pmc-release]
AID - 10.1089/hum.2005.16.584 [doi]
PST - ppublish
SO  - Hum Gene Ther. 2005 May;16(5):584-93. doi: 10.1089/hum.2005.16.584.