A NANOPARTICLE CD8 T CELL REGIMEN FOR CANCER THERAPY

Nanotarget, Llc, Morganville NJ

Investigators

Abstract

Despite much progress that has been made during past decades, current approaches in tumor immunotherapy remain less successful than desired. One major obstacle that prevents development of effective anti-tumor immunity is that most tumor cells lack the co-stimulatory signals essential for T cell activation and are protected by the suppressive cytokines such as TGF-beta. Recent studies by us and others have identified that CD8+ T cells ablated Cbl-b, a member of ubiquitin E3 ligase family, may overcome such an obstacle and thus provide a novel target for eliciting effective anti-tumor immunity against a broad spectrum of cancers. In this proposal, we present a plan to generate a modified version of nanoparticle to specifically silence Cbl-b in mouse and human CD8+ T cells. This nanoparticle system conjugated with single chain CD8 antibody is anticipated to deliver siRNA specifically to CD8+ T cells and facilitate siRNA release into the cytosol. We propose to use the improved nanoparticles to determine whether this targeted siRNA delivery system can silence Cbl-b in mouse or human CD8+ T cells in wild type mice or hu-SCID mice reconstituted with human PBMCs. We expect that availability of such vehicles will set up a solid foundation to proceed to next stage of study to test the multifunctional nanoparticle-based strategy in cancer therapy using mouse tumor models and in human clinical trials.