Accession Number:

ADA572313

Title:

Amplification of Anti-Tumor Immunity Without Autoimmune Complications

Descriptive Note:

Final rept. 15 Apr 2004-14 Apr 2007

Corporate Author:

WAYNE STATE UNIV DETROIT MI

Personal Author(s):

Report Date:

2007-05-01

Pagination or Media Count:

36.0

Abstract:

The hypothesis ss that inactivation of Treg cells accompanied by Neu DNA vaccination will overcome tolerance in BALB NeuT mice and inhibit spontaneous mammary tumorigenesis or reject an established s.c. tumor. The anticipated tumor growth inhibition may be achieved at the risk of developing autoimmunity. Thyroiditis will be measured to indicate the level of risk. We further hypothesize that DNA vaccines encoding both Neu and GITR ligand will stimulate effector T cells via conventional TCR interaction and inhibit suppressor activity via GITR signaling, thus inducing anll-turnor immunity without systemic Treg cell inactivation and the inadvertent induction of autoimmune diseases. To test the hypothesis that anti-tumor but not autoimmunity can be induced by DNA vaccine encoding NeuTM and GITRL, we will A construct and test DNA plasmids encoding NeuTM and GITRL and B perfom in vitro and in vivo testing of pVIVO-NeuTMGITRL. Toward sub-task B, we will 1 establish the read-outs for NeuTM DNA vaccination, to eluding humoral and cellular immunity, 2 establish the read-outs for autoimmune response by measuring immune reactivity to mTg and inflammatory infiltration in the thyroid and 3 measure anti -Neu md anti mTg reactivity in mice immunized with DNA encoding NeuTMGITRL

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE