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可启动、调节和指导针对人类患者肿瘤抗原的细胞溶解性T细胞介导的免疫应答。最近的临床试验已经证明，使用用自体肿瘤抗原（包括肿瘤细胞裂解物）离体致敏的DC诱导针对恶性疾病的临床上显著的免疫应答。新出现的证据表明，树突状细胞具有从肿瘤细胞获得抗原和在I类MHC分子的背景下“交叉呈递”这些外源获得的抗原以激活CTL应答的专门能力。针对确定的肿瘤抗原的单克隆抗体似乎增强树突状细胞的抗原摄取、加工和呈递。该I期提案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（DC）的肿瘤抗原加载的新策略作为自动化生产用于卵巢癌免疫治疗的完整的基于DC的疫苗的手段的可行性。

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.