Eliciting Autoimmunity to Ovarian Tumors in Mice by Genetic Disruption of T Cell Tolerance Mechanisms
Abstract
We are developing a mouse model for ovarian cancer that will allow monitoring of the in vivo activities of tumor-specific T cell clones as they encounter ovarian tumors in vivo. 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 in the murine ovarian tumor cell line lD8, epitope-tagged neu (designated neu (OT1/OT2)) should induce formation of aggressive ovarian adenocarcinomas that express the epitope tags and hence are recognizable by adoptively transferred TCR trangenic T cells. We successfully made the neu (OT1/OT2) expression construct, but found it to be overly immunogenic in vivo such that tumors were spontaneously rejected. Therefore, we derived a third generation lD8 tumor cell line that has a shorter tumor latency and decreased expression of MHC Class I, which should make it less immunogenic. 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. Finally, Cbl-b-/- mice have been obtained and are currently being backcrossed onto the B6 background for Aim 3.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA409619
Entities
People
- Brad H Nelson