Evaluation of Listeria Monocytogenes Based Vaccines for HER-2/neu in Mouse Transgenic Models of Breast Cancer
Abstract
HER-2/neu is a 185 kDa transmembrane protein that is a member of the epidermal growth factor family of receptors and is over expressed on 25-40% of all breast cancers. Five Listeria monocytogenes vaccines have been made consisting of fragments of HER-2/neu that are capable of stopping the growth of transplantable tumors in wild type FVB/N mice and can cause the eventual regression of about 30% of these tumors. Four of the vaccines contain no known epitopes yet each of the vaccines can lead to anti-HER-2/neu responses. Based on this we began mapping epitopes through cytotoxic T lymphocyte analyses. From this we have identified a novel epitope that falls into a different region of HER-2/neu than the previously identified epitope. We are studying these epitopes to see if there are similar levels of anti- tumor responses to both of these epitopes. In mice transgenic for rat HER-2/neu these vaccines cause a slowing in the growth of implanted NT-2tumors versus control mice. Regression is not seen in these mice because all of the Lm-LLO-HER-2/neu vaccinated mice scratch away their tumors. An autochthonous tumor experiment shows a much different result with the vaccines not all behaving identically but leading to different levels of protection. In this case Lm-LLO-EC3 does not delay the onset of tumor growth while each of the other four vaccines does with Lm-LLO-lC1 being significantly better than all of the other vaccines. We are currently attempting to determine if stromal elements in the mammary gland are involved in this difference.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2006
- Accession Number
- ADA450490
Entities
People
- Reshma Singh
Organizations
- University of Pennsylvania