Cationic Lipid/DNA/Antigen Complexes for Leukemia Vaccines

描述（由申请方提供）：本项目的总体目的是研究和开发一种新型急性髓细胞白血病疫苗。该产品，阳离子脂质-DNA复合物（CLDC），通过多种给药途径有效地广泛刺激先天性和适应性免疫系统，并作为一种有效的生物佐剂。先前的体外和体内研究表明，CLDC加抗原（CLDC/Ag）免疫可能被证明是AML患者的有效治疗方法，包括合作者就此提议收集的初步数据。虽然70%的AML患者在化疗后会进入缓解期，但这些患者中的60-80%会复发并死于疾病。因此，目前AML的许多治疗方法都是针对控制初始化疗后达到的最小残留疾病状态。当前项目的具体目标是优化递送途径，确认接种小鼠的正常造血，评价保护作用并鉴定赋予保护作用的特定细胞类型，并确定使用具有不同恶性肿瘤的肿瘤细胞系的治疗方案中肿瘤生长的动力学。肿瘤生长的动力学将通过作为稳定GFP转染子的32 D白血病细胞的流式细胞术来监测。拟议的实验将产生可行性数据，这将是一个刺激，建立这种新的方法在人类白血病免疫治疗的效用。这些研究还将直接比较免疫调节和疫苗方法作为利用CLDC/Ag的潜在治疗干预。鉴于AML患者的总体生存率较低，认为该方法提供了一个独特的机会，作为传统方法的替代疗法，以控制微小残留疾病并预防或延迟复发。

DESCRIPTION (provided by applicant): The overall purpose of this project is to investigate and develop a novel vaccine for Acute Myelogenous Leukemia. This product, cationic lipid-DNA complexes (CLDC), is effective via multiple administration routes in broadly stimulating the innate and adaptive immune system and serving as a potent biologic adjuvant. Previous in vitro and in vivo studies suggest that immunization with CLDC plus antigen (CLDC/Ag) may prove to be an effective therapeutic approach in the AML patient, including preliminary data collected by the collaborator on this proposal. Although 70% of AML patients will enter remission after chemotherapy, 60-80% of these patients will relapse and die of their disease. Thus, many current therapeutic approaches to AML are directed at controlling minimal residual disease states achieved after initial chemotherapy. The specific goals of the current project are to optimize route of delivery, confirm normal hematopoesis in vaccinated mice, evaluate protection and identify specific cell types that confer protection, and determine kinetics of tumor growth in therapeutic scenarios using tumor cell lines with varying malignancies. The kinetics of tumor growth will be monitored by flow cytometry of 32D leukemic cells that are stable GFP transfectants. The proposed experiments will generate feasibility data that will be a stimulus for establishing the utility of this novel approach for leukemia immunotherapy in humans. The studies will also provide a direct comparison of the immunomodulatory and vaccine approach as a potential therapeutic intervention utilizing CLDC/Ag. Given the poor overall survival rates of AML patients, it is believed that this approach offers a unique opportunity as an adjunctive therapy to traditional approaches to control minimal residual disease and prevent or delay relapse.