Enhanced Tumor Antigen Priming of Dendritic Cell Vaccine

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DESCRIPTION (provided by the applicant): Dendritic cells have been shown to initiate, regulate, and direct cytolytic T-cell-mediated immune responses against tumor antigens in human patients. Recent clincal trials have demonstrated induction of clinically significant immune responses against malignant diseases using DCs primed ex vivo with autologous tumor antigens including tumor cell lysates. Emerging evidence indicates that dendritic cells have a specialized capacity to acquire antigens from tumor cells and to "cross-present" these exogenously-acquired antigens in the context of class I MHC molecules for activation of CTL responses. Monoclonal antibodies against defined tumor antigens appear to enhance antigen uptake, processing and presentation by dendritic cells. The overall objective of this Phase I proposal is to demonstrate the feasibility of using new strategies for monoclonal antibody-mediated tumor antigen-loading of dendritic cells (DCs) in the AastromReplicell(TM) perfusion bioreactor system as a means for automated production of completed DC-based vaccines for immunotherapy of ovarian cancer.