Induction of Immunity to a Breast Cancer Associated Mucin in Transgenic Mice Expressing the Hurnan Antigen - A Preclinical Study
Abstract
The high incidence of breast cancer and the severity of the disease have created an urgent need for new and innovative forms of treatment. Mucin, the product of the MUC1 gene, has been identified as a breast cancer associated antigen in patients. We use a unique animal model of breast cancer to evaluate immunotherapeutic strategies to treat mice with the disease. Transgenic mice were prepared that express human mucin. The mice are naturally tolerant to human mucin. A malignant mouse breast cancer cell line (410.4) was modified to express human mucin (E3 cells). The cells were then further modified to express B7. 1, a co stimulatory molecule required for T cell activation, or to secrete immune-augmenting cytokines. Immunization of MUC1 transgenic mice with E3 cells modified to express B7.1 resulted in the induction of immunity to the breast cancer cells. Also, immunization with E3 cells modified to secrete IL-12 resulted in development of immunity to breast cancer in the MUC1 transgenic mice. Of special significance, MUC1 transgenic mice vaccinated with E3 cells modified to express B7.1 or to secrete IL- 12 did not develop autoimmune disease. The immunizations were without harm. In the forthcoming year, we plan to combine these two approaches to define the maximum tumor "load" in MUC1 transgenic mice that can be successfully treated with the modified cells. We also plan to continue our studies determine if the immunizations result in the development of autoimmune disease or are harmful to the MUC1 transgenic mice, and by implication, to breast cancer patients whose tumors express MUC1.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA381690
Entities
People
- Edward P. Cohen
Organizations
- University of Illinois at Chicago