Development of a Transgenic Mouse Model for Breast Cancer that is Optimized for the Study of T Cell-Based Therapeutic Strategies

摘要

We sought to develop a transgenic mouse model for breast cancer that would allow the in viva activities of tumor-specific T cell clones to be tracked through all stages of tumorigenesis and after various - immunotherapies. We 'tagged' the neu oncogene with two defined T cell epitopes which conferred recognition by OT-l and OT-II T cell receptor (TOR) transgenic T cells. When expressed as a transgenic in mammary epithelium, epitope-tagged neu designated neu(subOTl/OT2) was expected to induce mammary adenocarcinomas that express the epitope tags and hence are recognizable by OT-l and OT-II T cells. We generated three neu(subOTl/OT2) transgene-positive founder lines, and expression of neu(subOTl/OT2) in mammary epithelium was confirmed by Northern blot, western blot, and by immunological responses to the epitope tags. On its own, neu(subOTl/OT2) induced tumors in a minority of mice and with a long latency (12-16 months). Fortunately, when neu(subOTl/OT2) mice were crossed to mice expressing a mutant p53 transgene, tumors developed in the majority (718) of mice with a reasonable latency (7-9.5 months). We are currently using this model to analyze the T cell response to spontaneous mammary tumors and to develop novel immunotherapies for breast cancer. Thus, we fully accomplished the goals of this project.