Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 39, Issue 1, Pages 245-253Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2011.1004
Keywords
alpha-fetoprotein; dendritic cell; cytokine; AFP; T cells
Categories
Funding
- University of Pittsburgh Cancer Institute
- Shanghai Pu Jiang Talented Person Plan of China [07PJ14004]
- [RO1- CA104524]
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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.
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