A Novel Strategy of Immune Modulation to Treat Lung Cancer
Final rept. 15 Sep 2010-14 Sep 2011
CHARLESTON SOUTHERN UNIV SC
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The complement system is an important effector mechanism of innate and humoral immunity. Tumor cells are protected from complement by the expression of complement inhibitory proteins on their surface, and the downregulation or blockade of these inhibitory proteins may enhance anti-tumor antibody and T cell responses. The concept that we proposed to investigate was that siRNA mediated downregulation of a complement inhibitor on lung tumor cells will sensitize the tumor cells to complement and induce a protective immune response. We proposed to investigate an approach utilizing lung delivery of nanoparticles coated with an anti-MUC1 antibody to target delivery of complement inhibitor Crry siRNA to tumor cells. We prepared and characterized both nanoparticles and liposomes containing Crry siRNA that were also coated with anti-MUC1 mAb targeting antibody and a cell penetrating peptide. We demonstrated that the nanoparticles, but not liposomes, effectively downregulated Crry expression on lung tumor cells and increased complement deposition in vitro. However, the strategy failed to work in an in vivo model, and did not improve therapeutic outcome in a murine lung cancer model.
- Anatomy and Physiology
- Medicine and Medical Research