IMMUNOTHERAPY WITH CARCINOEMBRYONIC ANTIGEN PEPTIDE PULSED DENDRITIC CELLS

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，如诱导对肿瘤的免疫反应。本研究的目的是评估一种这样的免疫疗法的安全性和可行性，即用被称为树突状细胞(DC)的强大免疫刺激细胞(DC)接种于转移性CEA表达恶性肿瘤(如胃肠道、肺癌和乳腺癌)的患者。对患者进行筛查，以确保他们是免疫型HLA-A2，有表达CEA的肿瘤，以及有未能通过传统治疗的晚期或转移性疾病。符合条件的白血病患者，外周血单个核细胞与GM-CSF、IL-4共同培养产生DC，DC与CEA多肽混合。患者被分配到适当的剂量水平，在0、2、4和6周的第一天接受静脉和皮内注射树突状细胞。在免疫结束时进行重复的白细胞分离，以确定诱导的针对CEA的免疫反应。目标是招募18名可评估的患者，定义为那些接受了所有免疫接种并接受了最终白细胞分离的患者。我们已经完成了这项研究中患者的登记和治疗，现在正在跟踪他们的毒性、免疫反应和无进展生存。21名患者入选，15名患者可评估(其余患者没有接受所有免疫接种或进行后续白细胞分离)。没有直接与治疗有关的毒性反应。一名患者有轻微反应，一名病情稳定。目前正在对免疫应答数据进行分析。这项研究具有重要意义，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效力的第二阶段研究奠定了基础。我们计划将重点放在II期研究的微小残留病的设置上，包括局部胰腺癌切除后。

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.