425 translation of enhanced dendritic cell vaccines using a cid inducible cd40 receptor

CANCER-IMMUNOTHERAPY: SIGNAL TRANSDUCTION AND ANTIGEN PRESENTATION further improvements are needed to provide a breakthrough for GBM treatment To overcome the restraint of transient expression using nonviral vectors, we utilized Sleeping Beauty transposon vectors to achieve integration and sustained expression in GBM In parallel we used CpG oligodeoxynucleotides to stimulate potent anti-tumor immune responses To determine efficacy in an orthotopic model, syngeneic GL261-luciferase-stable tumor cells were implanted into the brains of C57BL/6 mice so that tumor progression and/or regression could be measured by bioluminescent imaging in vivo (see progression in Figure 1) We used intratumoral convectionenhanced delivery (CED) to infuse CpG oligodeoxynucleotides or Sleeping Beauty-based INF-gamma transposons into mice bearing intracranial GBM Either therapy alone minimally extended survival (p>0.05), but the combination of CpG plus INF-gamma gene transfer facilitated complete tumor regression and long-term survival in a significant fraction of mice (p