IMMUNOTHERAPY WITH CARCINOEMBRYONIC ANTIGEN PEPTIDE PULSED DENDRITIC CELLS

目的和理由：本提案的前提是， 临床有效的细胞介导的免疫应答， 表达肿瘤的胃肠癌、乳腺癌和肺癌 相关抗原CEA可以通过激活CEA特异性的 细胞毒性T细胞（CTL）。本方案拟进行I期临床试验 检查静脉注射的安全性和可行性， 自体外周血来源的树突状细胞（DC）脉冲 用代表HLA A-2限制性CEA CTL表位的肽， 局部晚期或转移性CEA患者HLA-A2诱导CTL- 表达对常规治疗难治的恶性肿瘤， 疗法 研究设计：本方案提出了一种开放标签、非受控剂量 采用三层剂量递增策略的递增初步研究。的 待测试的最高剂量对应于可以产生的最大数量的DC。 由从外周血收集的单核细胞产生 通过常规白细胞分离术分离出来的将对所有患者进行评估， 剂量限制性毒性和对治疗的免疫应答。

Purpose and Rationale: This proposal is based upon the premise that a clinically effective cell mediated immune response against gastrointestinal, breast, and lung cancers which express the tumor associated antigen CEA can be elicited by activation of CEA-specific cytotoxic T cells (CTL). This protocol proposes a phase I clinical trial to examine the safety and feasibility of the intravenous administration of autologous peripheral blood precursor derived dendritic cells (DC) pulsed with a peptide representing an HLA A-2 restricted CEA CTL epitope to induce CTL in HLA-A2 patients with locally advanced or metastatic CEA- expressing malignancies which have been refractory to conventional therapy. Study Design: This protocol proposes an open label, uncontrolled dose escalating pilot study with a three tiered dose escalation strategy. The highest dose to be tested corresponds to the largest number of DC that can be generated from mononuclear cells harvested from peripheral blood isolated by a routine leukapheresis. All patients will be evaluated for dose-limiting toxicity and immune responses to therapy.