Anti-tumor immunity induced by CDR3-based DNA vaccination in a murine B-cell lymphoma model

Monica Rinaldi, Daniela Fioretti, Sandra Iurescia, Emanuela Signori, Pasquale Pierimarchi, Davide Seripa, Giancarlo Tonon, Vito Michele Fazio

Research output: Contribution to journalArticle

Abstract

The idiotypic structure present on B-cell neoplasms is a tumor-specific antigen and an attractive target for immunotherapy. Here, the tumor protective effects recruited by CDR3-based DNA vaccines in the poorly immunogenic, highly aggressive 38C13 murine B-cell lymphoma model were evaluated. The regions belonging to the idiotypic VH and VL CDR3 sequences were chosen for the design of two synthetic mini-genes and arranged in high-level expression plasmids. Syngeneic C3H/HeN mice were immunized by intramuscular electroporation with pVHCDR3-IL-2 and pVLCDR3-IL-2 naked DNAs. This approach provided protection in about 60% of animals challenged with a 2-fold lethal dose of tumor cells, as opposed to non-survivors in control groups. Furthermore, a long-term survival was induced in these mice since they were still alive and tumor-free 4 months following tumor challenge. Analysis of the humoral immunity revealed the presence of antibodies reactive with the peptides encompassing the CDR3 sequences in the sera of vaccinated mice. Moreover, immune sera specifically reacted with the parental 38C13 tumor cells in flow cytometry assays, indicating that such immunization elicited anti-idiotypic antibodies. These findings provide a basis for exploring the use of CDR3-based DNA vaccines against B-cell lymphoma.

Original languageEnglish
Pages (from-to)279-284
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume370
Issue number2
DOIs
Publication statusPublished - May 30 2008

Keywords

  • Cancer vaccine
  • DNA vaccine
  • Lymphoma
  • Prophylactic naked DNA vaccination

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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