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Activation of cytotoxic T lymphocytes against CML28-bearing tumors by dendritic cells transduced with a recombinant adeno-associated virus encoding the CML28 gene.

Abstract
Induction of anti-tumor immune responses by dendritic cells (DCs) transduced with a recombinant adeno-associated virus type 2 (rAAV2) encoding tumor antigens is considered a promising approach for cancer vaccine development. CML28, a novel antigen with the properties of cancer/ testis (CT) antigens, is an attractive target for antigen-specific immunotherapy. Here we investigated the feasibility of inducing CML28-specific cytotoxic T lymphocyte (CTL) responses using DCs transduced with the rAAV2 vectors containing the CML28 gene (rAAV/CML28). Using an adenovirus-free packaging system, rAAV/CML28 was generated. The transduction efficiency of rAAV/CML28 in DCs increased in a multiplicity of infection (MOI)-dependent manner. The rAAV/CML28 transduction did not impair DC maturation, but even enhanced the CD80 expression. The rAAV/CML28-transduced DCs induced CML28-specific CTLs which exhibited a MHC class I-mediated antigen-specific lytic activity against CML28-bearing tumor cell lines (HepG2 and MCF-7) as well as the primary leukemia blasts. These findings suggest that rAAV/CML28-transduced DCs vaccine may serve as a feasible approach for the treatment of CML28-associated cancers.
AuthorsLi-Hua Xie, Fion Wan-Yee Sin, Samuel Chak-Sum Cheng, Ying-Kit Cheung, Kin-Tak Chan, Yi Xie, Yong Xie
JournalCancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 57 Issue 7 Pg. 1029-38 (Jul 2008) ISSN: 0340-7004 [Print] Germany
PMID18157497 (Publication Type: Journal Article)
Chemical References
  • Antigens, Neoplasm
  • Antigens, Surface
  • B7-1 Antigen
  • EXOSC5 protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • Exoribonucleases
  • Exosome Multienzyme Ribonuclease Complex
Topics
  • Adenoviridae (genetics)
  • Antigens, Neoplasm (biosynthesis, genetics, immunology)
  • Antigens, Surface (biosynthesis, genetics, immunology)
  • B7-1 Antigen (immunology)
  • Cell Line, Tumor
  • Dendritic Cells (immunology, metabolism)
  • Exoribonucleases (biosynthesis, genetics, immunology)
  • Exosome Multienzyme Ribonuclease Complex
  • Feasibility Studies
  • Genes, MHC Class I
  • Humans
  • Lymphocyte Activation
  • RNA, Messenger (biosynthesis)
  • RNA-Binding Proteins
  • T-Lymphocytes, Cytotoxic (immunology)

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