Amplification of Anti-Tumor Immunity Without Antoimmune Complications
Abstract
The hypothesis is that inactivation of Treg cells accompanied by Neu DNA vaccination will overcome tolerance in BALB NeuT mice and inhibit spontaneous matnmarytunorigenesis or reject an established s.c. tumor. The anticipated tumor growth inhibition maybe 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 GlTRligand will stimulate effectorT cells via conventional TCRinteraction and inhibit suppressor activity via GITR signaling, thus inducing anti-tumor 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 Neu- TM and GITRL% we will (A) construct and test DNAplasmids encoding NeuTM and GITRL and (B) perform in - vitro and in vivo testing of pVIVO-NeuTM!GlTRL. Toward sub-task B, we will (1) establish the read-outs for NeuTM DNA vaccination, including humorat and cellular immunity, (2) establish the read-outs for autoimmune response by measuring immune reactivity to mTg and inflammatory infiltration in the thyroid arid (3) measure anti-Neu and anti-mTg reactivity in mice immunized with DNA encoding NeuTM/GlTRL
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2005
- Accession Number
- ADA437183
Entities
People
- Wei-Zen Wei
Organizations
- Wayne State University