Enhanced Tumor Antigen Priming of Dendritic Cell Vaccine

描述（由申请人提供）：树突状细胞已被证明在人类患者中启动、调节和指导细胞溶解t细胞介导的针对肿瘤抗原的免疫反应。最近的临床试验已经证明，使用体外引物与自体肿瘤抗原（包括肿瘤细胞裂解物）一起的dc，可诱导临床显著的恶性疾病免疫应答。新出现的证据表明，树突状细胞具有从肿瘤细胞获取抗原的特殊能力，并在I类MHC分子的背景下“交叉呈现”这些外源获得的抗原，以激活CTL反应。针对特定肿瘤抗原的单克隆抗体似乎可以增强树突状细胞对抗原的摄取、加工和递呈。该I期计划的总体目标是证明在AastromReplicell（TM）灌注生物反应器系统中使用单克隆抗体介导的树突状细胞（DCs）肿瘤抗原负载新策略的可行性，作为自动化生产完整的基于dc的卵巢癌免疫治疗疫苗的手段。

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.