Eliciting Autoimmunity to Ovarian Tumors in Mice by Genetic Disruption of T Cell Tolerance Mechanisms
Abstract
We have developed a mouse model for ovarian cancer that allows monitoring of tumor-specific T cell clones as they encounter ovarian tumors in vivo. We "tagged" 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 rumor cell line ID8, epitope-tagged neu (designated neuOT1/OT2) induces the formation of aggressive ovarian adenocarcinomas that express the epitope tag and hence are recognizable by adoptively transferred TCR trangenic T cells. We successfully made the neuOT1/OT2expression construct and stably expressed it in an aggressive subclone of the ID8 cell line, designated 1D8-G7, which was derived by serial in vivo passage of the original ID8 line. When injected introperitoneally into syngenic mice, 1D8-G7 cells expressing neuOT1/OT-II give rise within one month to disseminated ovarian cancer with extensive ascites (Aim 1). CD8+ (OT-I) T cells specific for neuOT1/OT-II proliferate extensively after adoptive transfer into tumour-bearing hosts and, remarkably, induce complete tumour regression within 10 days in a dose-dependent manner (Aim 2). In the next year, we will test whether the dose-dependency of this response can be mitigated by use of autoimmune-prone Cbl-b-deficient CD8+ T cells (Aim 3).
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2006
- Accession Number
- ADA462679
Entities
People
- Brad H Nelson
Organizations
- BC Cancer Agency