PMID- 21491085
OWN - NLM
STAT- MEDLINE
DCOM- 20110909
LR  - 20211020
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 39
IP  - 1
DP  - 2011 Jul
TI  - Lentivirally engineered dendritic cells activate AFP-specific T cells which 
      inhibit hepatocellular carcinoma growth in vitro and in vivo.
PG  - 245-53
LID - 10.3892/ijo.2011.1004 [doi]
AB  - alpha-fetoprotein (AFP), a tumor-associated antigen for hepatocellular carcinoma 
      (HCC), is an established biomarker for HCC. In this study, we created a 
      lentivirus expressing the AFP antigen and investigated the anti-tumor activity of 
      AFP-specific CD8+ T cells, with and without CD4+ T cells, which were activated by 
      either AFP peptide-pulsed or Lenti-AFP-engineered Dendritic cells (DCs) in vitro 
      and in vivo. AFP-specific T cells could efficiently kill HepG2 HCC cells, and 
      produced IL-2, IFN-gamma, TNF-alpha, perforin and granzyme B, with minimal production of 
      IL-10 (a negative regulator of T cell activation). Both strategies activated 
      AFP-specific T cells, but the lentiviral strategy was superior by several 
      measures. Data also support an impact of CD4+ T cells in supporting anti-tumor 
      activity. In vivo studies in a xenograft HCC tumor model also showed that 
      AFP-specific T cells could markedly suppress HCC tumor formation and morbidity in 
      tumor-bearing nude mice, as well as regulate serum levels of related cytokines 
      and anti-tumor molecules. In parallel with human in vitro T cell cultures, the in 
      vivo model demonstrated superior anti-tumor effects and Th1-skewing with 
      Lenti-AFP-DCs. This study supports the superiority of a full-length antigen 
      lentivirus-based DCs vaccine strategy over peptides, and provides new insight 
      into the design of DCs-based vaccines.
FAU - Liu, Yang
AU  - Liu Y
AD  - Shanghai 10th People's Hospital Affiliated to Tongji University, Shanghai 200072, 
      PR China. yliu6633@yahoo.com.cn
FAU - Butterfield, Lisa H
AU  - Butterfield LH
FAU - Fu, Xiaohui
AU  - Fu X
FAU - Song, Zhenshun
AU  - Song Z
FAU - Zhang, Xiaoping
AU  - Zhang X
FAU - Lu, Chongde
AU  - Lu C
FAU - Ding, Guanghui
AU  - Ding G
FAU - Wu, Mengchao
AU  - Wu M
LA  - eng
GR  - R01 CA104524/CA/NCI NIH HHS/United States
GR  - R01- CA104524/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110413
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Cytokines)
RN  - 0 (Epitopes)
RN  - 0 (Peptides)
RN  - 0 (alpha-Fetoproteins)
SB  - IM
MH  - Animals
MH  - Carcinoma, Hepatocellular/*immunology/physiopathology
MH  - Cell Line, Tumor
MH  - Cytokines/metabolism
MH  - Cytotoxicity, Immunologic/immunology
MH  - Dendritic Cells/*immunology
MH  - Disease Models, Animal
MH  - Epitopes/immunology
MH  - Gene Transfer Techniques
MH  - Genetic Vectors/*genetics
MH  - HEK293 Cells
MH  - Hep G2 Cells
MH  - Humans
MH  - Lentivirus/*genetics
MH  - Liver Neoplasms/*immunology/physiopathology
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Mice, Nude
MH  - Peptides/immunology
MH  - T-Lymphocytes/*immunology
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - alpha-Fetoproteins/chemistry/genetics/*immunology
PMC - PMC3457796
MID - NIHMS408020
EDAT- 2011/04/15 06:00
MHDA- 2011/09/10 06:00
PMCR- 2012/09/25
CRDT- 2011/04/15 06:00
PHST- 2010/11/04 00:00 [received]
PHST- 2010/12/20 00:00 [accepted]
PHST- 2011/04/15 06:00 [entrez]
PHST- 2011/04/15 06:00 [pubmed]
PHST- 2011/09/10 06:00 [medline]
PHST- 2012/09/25 00:00 [pmc-release]
AID - 10.3892/ijo.2011.1004 [doi]
PST - ppublish
SO  - Int J Oncol. 2011 Jul;39(1):245-53. doi: 10.3892/ijo.2011.1004. Epub 2011 Apr 13.