Accession Number:

ADA383985

Title:

The Use of Her2/neu-Specific Genetic Vaccines for the Prevention and Treatment of Breast Cancer

Descriptive Note:

Annual rept. 1 Jul 1998-30 Jun 1999

Corporate Author:

NORTH CAROLINA UNIV AT CHAPEL HILL

Personal Author(s):

Report Date:

1999-07-01

Pagination or Media Count:

12.0

Abstract:

We are investigating the feasibility of using HER2neu encoding genetic vaccines to elicit potent CD4 and CD8 T cell reactivity for the prevention and treatment of breast cancer. Two strategies of genetic vaccination, each with distinct advantages, will be assessed. The first strategy entails the use of alphavirus Venezuelan equine encephalitis virus VEE-replicons which selectively infect dendritic cells in vivo. Dendritic cells are characterized by an exceptional capacity to initiate and establish potent T cell immunity. Our second strategy is to employ a plasmid DNA pDNA vaccine encoding HER2neu. pDNA vaccination has been shown to be effective in inducing persistent T cell responses in various model systems. VEE-replicon and pDNA vaccines encoding cytokines such as IL-l2 and IL-18, will also be used to enhance anti-HER2neu-specific CD4 Thi cell and CD8 CTL activity. To directly assess the efficacy of our approach to prevent tumor cell growth andor eradicate established tumors, we will employ mice transgenic for a rat HER2neu gene. These mice develop mammary tumors and pulmonary metastatic lesions. Furthermore, we will use mice transgenic for an HLA-A2.1 molecule to assess CD8 CTL reactivity to HER2neu-specific peptide epitopes which have been proposed as targets for immunotherapy in a clinical setting.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE