Accession Number : ADA457685


Title :   Amplification of Anti-Tumor Immunity Without Autoimmune Complications


Descriptive Note : Annual rept. 15 Apr 2005-14 Apr 2006


Corporate Author : WAYNE STATE UNIV DETROIT MI


Personal Author(s) : Wei, Wei-Zen


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA457685


Report Date : MAY 2006


Pagination or Media Count : 17


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.


Descriptors :   *THYROID GLAND , *AMPLIFICATION , *IMMUNITY , *AUTOIMMUNIZATION , DEOXYRIBONUCLEIC ACIDS , CHROMOSOMES , ANTIGENS , THYROGLOBULIN , LUCIFERASE , IMMUNIZATION , INFLAMMATION , MICE , RESIDUALS , GENES


Subject Categories : BIOCHEMISRTY
      ANATOMY AND PHYSIOLOGY
      MEDICINE AND MEDICAL RESEARCH


Distribution Statement : APPROVED FOR PUBLIC RELEASE