Amplification of Anti-Tumor Immunity Without Autoimmune Complications
Abstract
The goal is to combine Treg inactivation with Nau DNA vaccination to inhibit tumor growth in BALB NeuT mice without inducing excessive autoimmunity such as experimental autoimmune thyroiditis (EAT). We established a test system to access in the same animal the effect of tumor regression and mouse thyroglobulin immunization and observed a synergy between anti-neu and anti-mTg immunity. We tested the vaccination efficacy of pE2TM (encoding human Her-2 ECO and TM domains) combined with pGITRL. Mice co-activated with these two plasmid DNA showed comparable anti-neu and anti-tumor immunity as those receiving pneu TM and pGM-CSF. The co-stimulatory activity of GITRL/CITR inferaction may account for this level of activity but stimulation of GITR may not affect Treg activity as demonstrated in several recent reports. We will use the residual resources to test a new strategy to enhance anti-tumor immunity without excessive systemic modulation of Treg i.e. expression of foreign antigens in the tumor by intratumoral DNA electroporation. We showed the expression of luciferase in the tumor for 17 days or longer. The treatment schedule will be optimized to achieve high level sustained expression and tumor growth will be monitored.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2006
- Accession Number
- ADA457685
Entities
People
- Wei-Zen Wei
Organizations
- Wayne State University