The Use of Venezuelan Equine Encephalitis Encoding the Her-2/neu Tumor Associated Antigen for the Prevention and Treatment of Breast Cancer
Abstract
Our project has focused developing a vaccination protocol using Venezuelan Equine Encephalitis (VEE) replicons (VRP) encoding the Her-2/neu tumor associated antigen to mediate anti tumor immunity in Her-2/neu transgenic (Tg) mice. Initial work demonstrated that vaccination with the VRP encoding full-length Her2/neu elicited robust Her2/neu-specific cytotoxic T lymphocyte (CTL) reactivity in the non-Tg parental strain (FVB/n) of mice (Fig. 1). However, no significant Her2/neu-specific CTL reactivity was detected in cultures prepared from the FVB/neu Tg mice (Fig. 1). The results demonstrated that an element of self tolerance to Her2/neu exists in the transgenic mice. We postulated that due to the size of the cDNA encoding full length Her2/neu (greater than 4 kb), levels of in vivo expression were not sufficient to elicit a CD8+ T cell response in FVB/neu Tg mice. Accordingly, a VRP encoding the extracellular and transmembrane domains (VRP-EC/TMD) spanning approximately 2 kb was established. More recently, a VRP encoding the intracellular domain (VRP-ICD) has also been generated. Notably, a comparable frequency of IL-2 and IFNy secreting T cells following stimulation with Her2/neu expressing NT2.5 tumor cells' was detected in cultures prepared from either FVB/n or FVBIneu Tg mice (Fig. 2). These results demonstrated that vaccination with VRP-EC/TMD could elicit significant Her2/neu-specific T cell reactivity despite tolerance to the neo-self antigen.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2003
- Accession Number
- ADA416667
Entities
People
- Brian R. Long
- Roland M. Tisch
Organizations
- University of North Carolina at Chapel Hill