Novel MHC Class II Breast Cancer Vaccine Using RNA Interference (RNAi) to Down Regulate Invariant Chain (Ii); Annual summary 1 May 2003-30 Apr 2007

摘要

Our goal is to induce a strong CD4+ T cell response against tumor antigens by preferentially presenting endogenous tumor antigens via class II major histocompatibility complex molecules (MHC II). MHC II can present endogenous tumor antigens if expressed in the absence of Invariant chain (II). We have up-regulated MHCII and down regulated II without affecting MHC II expression in tumor cells. Using the key transcription factor class II trans-activator (CIITA) we have coordinately up-regulated all class II MHC molecules (DR, DP, DQ) and associated molecules such as the Invariant chain in a Human mammary carcinoma (MCF10). We have successfully down regulated the invariant chain in MCF10 cells, up regulated for MHC II, using retroviral vectors that express siRNAs as hairpin loops. Immuno-fluorescence shows no down regulation of MHC II molecules on the cell surface after II was down regulated. We will test the ability of our vaccine to present tumor antigen by observing whether these cells can stimulate HER2/neu restricted CD4+ or CD8+ T cells. These tumor cells could be used as a vaccine stimulating both CD4+ and CD8+ T cells in close proximity inducing a powerful long-term immune response against tumor sharing common tumor antigen with the vaccine.