Development of a Transgenic Mouse Model for Breast Cancer that is Optimized for the Study of T Cell-Based Therapeutic Strategies
Abstract
Our goal is to develop a transgenic mouse model for breast cancer that will allow the in vivo activities of tumor-specific T cell clones to be tracked at all stages of tumorigenesis and after various immune interventions. We proposed to "tag' the neu oncogene with two defined T cell epitopes so as to confer recognition by available T cell receptor (TCR) transgenic T cells. When expressed as a transgene in mammary epithelium, epitope-tagged neu (designated neu OT1/OT2) should induce formation of aggressive mammary adenocarcinomas that express the epitope tags and hence are recognizable by adoptively transferred TCR trangenic T cells. This past year, we have obtained five neuOTl/OT2 transgene-positive founders, which have been bred to produce multiple female offspring. Expression of neu in mammary epithelium is being evaluated, and mice are being monitored for mammary tumorigenesis. Meanwhile, we have commenced adoptive T cell transfer experiments using a convenient, transplantable lymphoma model, and have discovered signaling differences between T cells that are responding to antigen-positive tumors versus the same antigen delivered with adjuvant. Thus, Aim I and much of Aim 2 have been successfully completed, and we are beginning to obtain novel insights into T cell responses in the tumor environment.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA406806
Entities
People
- Brad H Nelson