Survivin-DNA vaccine for active anti-tumor immunotherapy

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The overall objective is to establish the new paradigm that novel, oral DNA vaccines against the inhibitor of apoptosis protein, survivin, are sufficiently robust to promote both tumor cell apoptosis and collapse of tumor-associated angiogenesis leading to eradication of tumor metastases. We will establish proof of concept in a syngeneic model of neuroblastoma, a therapeutically challenging pediatric tumor. The specific aims are: first, to construct a newly designed oral DNA vaccine encoding H-2Kk and H-2Dd predicted epitopes of survivin and to characterize its biological functions; second, to evaluate efficacy in a syngenic neuroblastoma mouse model to prevent dissemination of tumor metastases in a prophylactic setting and therapeutic setting; third, to investigate immunological mechanisms involved in survivin-based DNA vaccine-induced CTL responses triggering suppression of angiogenesis and induction of tumor cell apoptosis.