DNA Vaccination Against Metastatic Breast Cancer
Abstract
HER2/neu over-expression is found in 30-40% of breast cancer biopsy and is indicative of metastasis and poor prognosis (1). Although significant advances have been made in the treatment of breast cancer, once metastasis has occurred the possibility of a complete cure is unlikely (1). A vaccine targeting HER2/neu could have significant therapeutic and preventative application by controlling the growth and spread of highly aggressive HER2/neu+ cells (2). The newest type of tumor vaccines, gene vaccines, encode the DNA sequence for tumor antigens. Bacterial expression plasmids containing tumor gene sequences have been shown to induce strong anti-tumor immunity in mice (3). Although gene vaccines have shown effectiveness in clinical trials for infectious diseases (4), it is essential to demonstrate pre-clinical effectiveness for anti-tumor vaccines before clinical testing can begin (5-7). We have shown that vaccination of mice with a novel plasmid expressing the DNA sequence for HER2/neu protected mice from tumor incidence when challenged with a HER2/neu+ murine breast tumor cell line injected directly into mammary tissue. We also found that vaccination was able to reduce metastasis when the tumor was injected intravenously, a model of tumor metastasis. The plasmid we used for vaccination, called ELVIS, was created by Chiron Corp. (Emeryville, CA) and incorporates unique properties of Sindbis vims, a non-pathogenic alphavims (8). Recently, Chiron Corp. has provided us with a more advanced version of their plasmid called ELVIS2, and we have shown it to be even more powerful than the original ELVIS when injected before mice a challenged with a tumor (protective vaccination). However, ELVIS2-neu was not able to prolong the life of mice when vaccinated followed surgical removal of a primary neu+ breast tumor (surgery model) or when vaccination was performed on a tumor bearing mouse (race model). Thus, different strategies are required in our two therapeutic vaccination 7
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADB283918
Entities
People
- Lawrence B. Lachman
Organizations
- United States Army Medical Research and Development Command