Lentivirally engineered dendritic cells activate AFP-specific T cells which inhibit hepatocellular carcinoma growth in vitro and in vivo

  • Authors:
    • Yang Liu
    • Lisa H. Butterfield
    • Xiaohui Fu
    • Zhenshun Song
    • Xiaoping Zhang
    • Chongde Lu
    • Guanghui Ding
    • Mengchao Wu
  • View Affiliations

  • Published online on: April 13, 2011     https://doi.org/10.3892/ijo.2011.1004
  • Pages: 245-253
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Abstract

α-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-γ, TNF-α, 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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July 2011
Volume 39 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Liu Y, Butterfield LH, Fu X, Song Z, Zhang X, Lu C, Ding G and Wu M: Lentivirally engineered dendritic cells activate AFP-specific T cells which inhibit hepatocellular carcinoma growth in vitro and in vivo. Int J Oncol 39: 245-253, 2011
APA
Liu, Y., Butterfield, L.H., Fu, X., Song, Z., Zhang, X., Lu, C. ... Wu, M. (2011). Lentivirally engineered dendritic cells activate AFP-specific T cells which inhibit hepatocellular carcinoma growth in vitro and in vivo. International Journal of Oncology, 39, 245-253. https://doi.org/10.3892/ijo.2011.1004
MLA
Liu, Y., Butterfield, L. H., Fu, X., Song, Z., Zhang, X., Lu, C., Ding, G., Wu, M."Lentivirally engineered dendritic cells activate AFP-specific T cells which inhibit hepatocellular carcinoma growth in vitro and in vivo". International Journal of Oncology 39.1 (2011): 245-253.
Chicago
Liu, Y., Butterfield, L. H., Fu, X., Song, Z., Zhang, X., Lu, C., Ding, G., Wu, M."Lentivirally engineered dendritic cells activate AFP-specific T cells which inhibit hepatocellular carcinoma growth in vitro and in vivo". International Journal of Oncology 39, no. 1 (2011): 245-253. https://doi.org/10.3892/ijo.2011.1004