Efficient generation of cytotoxic T lymphocytes against cervical cancer cells by adeno-associated virus/human papillomavirus type 16 E7 antigen gene transduction into dendritic cells

Maurizio Chiriva-Internati, Yong Liu, Emanuela Salati, Weiping Zhou, Zhiqing Wang, Fabio Grizzi, Juan J. Roman, Seah H. Lim, Paul L. Hermonat

Research output: Contribution to journalArticlepeer-review

Abstract

Adeno-associated virus (AAV) is able to efficiently deliver a cytokine gene into dendritic cells (DC). Improvements in T cell priming by DC might be effected by the delivery of antigen genes into DC, resulting in continuous protein expression, as most proteins have short half-lives. In this study, a recombinant AAV vector containing the human papillomavirus (HPV)-16 E7 gene was used to pulse/infect DC and compared to the pulsing of DC by the lipofection of bacterially produced E7 protein. Pulsing of DC with AAV/antigen (Ag) gene was found to be superior to pulsing with protein in six different assay systems: (1) the level of antigen transfer into DC as determined by intracellular staining; (2) the level of MHC class I-restricted killing in cytotoxic T lymphocyte (CTL) assays; (3) the level of IFN-γ expression; (4) the level of DC-T cell priming clusters generated; (5) the level of CD80 and CD83 expression on DC; and (6) in the resulting CD8:CD4 ratio. Finally, AAV/Ag gene pulsing resulted in strong CTL activity after only 7 days of priming. These data suggest that AAV vectors may offer advantages over the commonly used protein-pulsing technique and that AAV vectors may be useful for the stimulation of CTL activity and adoptive immunotherapy protocols.

Original languageEnglish
Pages (from-to)30-38
Number of pages9
JournalEuropean Journal of Immunology
Volume32
Issue number1
DOIs
Publication statusPublished - 2002

Keywords

  • Adeno-associated virus
  • Cervical cancer
  • Dendritic cell
  • Human papillomavirus E7
  • Integration

ASJC Scopus subject areas

  • Immunology

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