Enhanced Tumor Antigen Priming of Dendritic Cell Vaccine

描述(由申请人提供)：树突状细胞已经被证明在人类患者中启动、调节和引导细胞溶解T细胞介导的针对肿瘤抗原的免疫反应。最近的临床试验表明，用包括肿瘤细胞裂解物在内的自体肿瘤抗原体外启动的DC可以诱导临床上显著的抗肿瘤免疫反应。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性获得的抗原，以激活CTL反应。针对特定肿瘤抗原的单抗似乎能增强树突状细胞对抗原的摄取、处理和呈递。这一第一阶段提案的总体目标是论证在AstromReplicell(TM)灌注生物反应器系统中使用单抗介导的树突状细胞(DC)肿瘤抗原负载的新策略作为自动化生产用于卵巢癌免疫治疗的完整DC疫苗的方法的可行性。

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.