DEXASOME BASED IMMUNOTHERAPY OF LUNG CANCER

研究人员提出了一项I/II期临床试验， 安全性、可行性、临床和免疫活性， 一种新的、广泛适用的主动免疫疗法：肿瘤抗原 装载自体帝萨体。Dexosomes是从树突状细胞释放的囊泡， 表达必需的人类白细胞抗原（HLA）的细胞， 共刺激分子和粘附分子诱导T细胞免疫 应答这项拟议中的研究将是第一个测试 负载肽抗原帝萨体将引发抗原特异性 癌症患者的CD 8 + T细胞反应。在动物模型中，肿瘤抗原 装载的帝萨体诱导免疫应答，可以保护免受肿瘤 挑战并导致肿瘤消退，并且比 树突状细胞此外，由于帝萨体代表无细胞物质， 与树突状细胞相比， 免疫疗法，如更容易处理，储存和便携性，没有问题 关于可行性。一种可能的策略是最初测试临床和 帝萨体在患者中的免疫活性是靶向具有以下特征的患者： 晚期肺癌因为晚期肺癌的预后很差， 其他疗法如免疫疗法值得评价。六十四 %的非小细胞肺腺癌表达法师-3或法师-4，80 %的非小细胞鳞状细胞癌表达法师-3或法师-4。 法师-3和法师-4的HLA-A2限制性肽表位，其可以是 已经鉴定了由肿瘤抗原特异性T细胞识别的抗体。的 因此，申请人建议确定以下物质的安全性和可行性： 产生和施用负载HLA-A2限制性的自体帝萨体 法师-3和法师-4的肽表位。申请人建议评估 临床应答并分析法师-3和法师-4特异性T细胞应答 在晚期肺癌患者中表达MAGE 3或MAGE 4。这 临床试验将成为进一步试验的背景， 证明了基于帝萨体的免疫学和临床益处， 免疫疗法

The investigators propose a phase I/II clinical trial to explore the safety, feasibility, and clinical and immunologic activity of a potent, novel, and broadly applicable form of active immunotherapy: tumor antigen loaded autologous dexosomes. Dexosomes are vesicles released from dendritic cells that express the necessary Human Leukocyte Antigens (HLA), co-stimulatory, and adhesion molecules required to induce T cell immune responses. This proposed study would be the first clinical trial to test the hypothesis that peptide antigen loaded dexosomes will elicit antigen specific CD8+ T cell responses in patients with cancer. In animal models, tumor antigen loaded dexosomes induced immune responses that could protect against tumor challenge and cause tumor regression and were remarkably more potent than dendritic cells. In addition, because dexosomes represent cell free material, they have potential clinical advantages over dendritic cell-based immunotherapy, such as easier handling, storage and portability and no concerns about viability. One possible strategy to initially test the clinical and immunologic activity of dexosomes in patients is to target patients with advanced lung cancer. Because the prognosis for advanced lung cancer is poor, additional therapies such as immunotherapy warrant evaluation. Sixty-four percent of non-small cell lung adenocarcinomas express MAGE-3 or MAGE-4, and 80 percent of non-small cell squamous cell carcinomas express MAGE-3 or MAGE-4. HLA-A2 restricted peptide epitopes of both MAGE-3 and MAGE-4 that can be recognized by tumor antigen specific T cells have been identified. The applicants therefore propose to determine the safety and feasibility of generating and administering autologous dexosomes loaded with HLA-A2 restricted peptide epitopes of MAGE-3 and MAGE-4. The applicants propose to evaluate the clinical response and to analyze the MAGE-3 and MAGE-4 specific T cell response in patients with advanced lung cancers that express MAGE3 or MAGE4. This clinical trial will form the background for further trials designed to demonstrate both immunology and clinical benefits of dexosome-based immunotherapy.