Accession Number:

ADA409619

Title:

Eliciting Autoimmunity to Ovarian Tumors in Mice by Genetic Disruption of T Cell Tolerance Mechanisms

Descriptive Note:

Annual rept. 1 Aug 2001-31 Jul 2002

Corporate Author:

VIRGINIA MASON RESEARCH CENTER SEATTLE WA

Personal Author(s):

Report Date:

2002-08-01

Pagination or Media Count:

10.0

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 OT1OT2 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 OT1OT2 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.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE