IMMUNOTHERAPY WITH CARCINOEMBRYONIC ANTIGEN PEPTIDE PULSED DENDRITIC CELLS

癌胚抗原肽脉冲树突细胞的免疫治疗

• 批准号: 6415295
• 负责人: HERBERT KIM LYERLY
• 金额: $ 29.31万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-01 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6415295
• 关键词: MHC class I antigen; carcinoembryonal antigen; clinical research; clinical trial phase I; cytotoxic T lymphocyte; cytotoxicity; dendritic cells; dosage; drug adverse effect; drug screening /evaluation; human subject; human therapy evaluation; immunocytochemistry; immunotherapy; intravenous administration; neoplasm /cancer immunotherapy

Because metastatic solid organ tumors are often incurable with standard approaches, other strategies such as inducing immune responses against the tumor are being explored. The purpose of this study is to evaluate the safety and feasibility of one such form of immunotherapy, vaccinations with potent immune stimulating cells called dendritic cells (DC) loaded with a peptide fragment of a tumor- associated protein, carcinoembryonic antigen (CEA) for patients with metastatic CEA expressing malignancies such as gastrointestinal, lung, and breast cancers. Patients are screened to assure that they are immune type HLA-A2, have a tumor that expresses CEA, and have advanced or metastatic disease that has failed conventional therapy. Eligible patients are leukapheresed, their peripheral blood mononuclear cells are cultured with GM-CSF and IL-4 to produce DC, and the DC are mixed with CEA peptide. Patients are assigned to the appropriate dose levels and receive intravenous and intradermal injections of the dendritic cells on day one of weeks 0, 2, 4, and 6. A repeat leukapheresis is performed at the end of the immunizations to determine the immune response induced against CEA. The goal was to enroll 18 evaluable patients, defined as those who received all immunizations and underwent the final leukpaheresis. We have completed enrollment and treatment of the patients on this study and are now following them for toxicities, immune responses, and progression-free survival. Twenty one patients were enrolled and 15 were evaluable (the remainder did not receive all the immunizations or undergo the follow-up leukpaheresis). There were no toxicities directly referable to the treatments. One patient had a minor response and one stable disease. The immunologic response data is being analyzed presently. This study is significant in that it demonstrates the safety and feasibility of this approach and provides the groundwork for phase II studies of the immunologic efficacy of these vaccines. We plan to focus on settings of minimal residual disease for the phase II studies, including after resection of localized pancreatic cancer.

由于转移性实体器官肿瘤通常无法用标准方法治愈，因此正在探索其他策略，例如诱导针对肿瘤的免疫反应。本研究的目的是评估一种免疫疗法的安全性和可行性，即用强效免疫刺激细胞（称为树突状细胞（DC））进行疫苗接种，该细胞负载肿瘤相关蛋白、癌胚抗原（CEA）的肽片段，用于表达胃肠道癌、肺癌和乳腺癌等转移性 CEA 的恶性肿瘤患者。对患者进行筛查，以确保他们是 HLA-A2 免疫型、患有表达 CEA 的肿瘤、并且患有常规治疗失败的晚期或转移性疾病。对符合条件的患者进行白细胞分离，将其外周血单核细胞与GM-CSF和IL-4一起培养以产生DC，并将DC与CEA肽混合。患者被分配到适当的剂量水平，并在第 0、2、4 和 6 周的第一天接受树突状细胞的静脉内和皮内注射。在免疫结束时进行重复白细胞分离术以确定针对 CEA 诱导的免疫反应。目标是招募 18 名可评估患者，即接受所有免疫接种并接受最终白细胞分离术的患者。我们已经完成了这项研究中患者的入组和治疗，现在正在跟踪他们的毒性、免疫反应和无进展生存期。 21 名患者入组，15 名可评估（其余患者未接受所有免疫接种或进行后续白细胞去除术）。没有与治疗直接相关的毒性。一名患者反应轻微，一名患者病情稳定。目前正在分析免疫反应数据。这项研究的意义重大，因为它证明了这种方法的安全性和可行性，并为这些疫苗的免疫功效的 II 期研究提供了基础。我们计划在 II 期研究中重点关注微小残留病的情况，包括局部胰腺癌切除后的情况。