Anti-tumor immunity induced by CDR3-based DNA vaccination in a murine B-cell lymphoma model
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- 作者：Monica Rinaldi ; Daniela Fioretti ; S ; ra Iurescia ; Emanuela Signori ; Pasquale Pierimarchi ; Davide Seripa ; Giancarlo Tonon ; Vito Michele Fazio
- 关键词：DNA vaccine ; Cancer vaccine ; Lymphoma ; Prophylactic naked DNA vaccination
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2008
- 出版时间：30 May 2008
- 年：2008
- 卷：370
- 期：2
- 页码：279-284
- 全文大小：456 K
文摘
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.