Development of a Transgenic Mouse Model for Breast Cancer that is Optimized for the Study of T Cell-Based Therapeutic Strategies
Annual rept. 15 May 2000-14 May 2001
VIRGINIA MASON RESEARCH CENTER SEATTLE WA
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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 OT1OT2 should induce formation of aggressive mammary adenocarcinomas that express the epitope tags and hence are recognizable by adoptively transferred TOR trangenic T cells. To date, we have successfully attached the OT1 and OT2 epitope tags to the neu oncogene and shown by in vitro as sasthat1 neu OTlOT2 is indeed recognized by OT1 - and OT2-specific TCR transgenic T cells, and 2 neu OT1OT2 retains its transforming properties. neu OTl 0T2 was then placed downstream of the MMTV promoter, and transgenic mice were generated. Of 13 pups born, one transgene-positive male founder was obtained and is currently being bred to multiple females. Thus, Aim 1 and a portion of Aim 2 have been successfully completed on schedule and without any major difficulties.
- Anatomy and Physiology
- Medicine and Medical Research