Induction of Immunity to a Breast Cancer Associated Mucin in Transgenic Mice Expressing the Human Antigen - A preclinical Study.
Abstract
Polymorphic epithelial mucin (PEM), the product of the MUC1 gene, is expressed in an aberrant form by human breast cancer cells. It is a known, potential target for cytotoxic T lymphocytes of patients with the disease. Cloning of the MUC1 gene and the development of transgenic mice that form human PEM, as well as the genetic modification of mouse breast cancer cells to express human PEM (E3 cells) provides an important model system for the investigation of various means of inducing immunity to PEM. The system mimics as closely as possible the induction of immunity to PEM in breast cancer patients. In the past year, we found that E3 cells modified for the secretion of lL-12 were poorly tumorigenic in MUC1 transgenic mice, and that immunization with X-irradiated lL-12-secreting E3 cells resulted in immunity to breast cancer. We also found that immunization with E3 modified to express B7. 1, a co stimulatory molecule required for T cell activation, resulted in prolongation of survival of MUC1 transgenic mice with breast cancer. Autoimmunity failed to develop in the transgenic mice immunized with the MUC-1 positive cells modified to express B7. 1. We expanded our study to evaluate the immunotherapeutic benefit of a DNA-based breast cancer vaccine, and are developing transgenic mice that express both alleles of the MUC1 gene.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADA358084
Entities
People
- Edward P. Cohen
Organizations
- University of Illinois at Chicago