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Targeted Therapy of Mesothelioma and Development of Bloo

间皮瘤的靶向治疗和 Bloo 的发展

基本信息

批准号：
7338579
负责人：
RAFFIT HASSAN
金额：
--
依托单位：
DIVISION OF BASIC SCIENCES - NCI
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7338579
关键词：
Targeted Therapy Mesothelioma Development Bloo

项目摘要

Our clinical research is focused on targeted therapy of mesothelin expressing cancers. Mesothelin is a 40-kDa cell surface glycoprotein that is present on normal mesothelial cells lining the pleura, pericardium and peritoneum. It is highly expressed in patients with mesothelioma and ovarian and pancreatic cancers. We are conducting clinical trails of the anti-mesothelin immunotoxin SS1P at the NCI. In the Phase I trial we treated 34 patients (20 mesothelioma; 12 ovarian cancer; 2 pancreatic cancer) and anti-tumor activity was noted in several patients. Based on these results we are about to start a Phase II clinical trial of SS1P in patients with mesothelioma. Since our laboratory studies show marked synergy between SS1P and chemotherapy this phase II study will evaluate the activity of SS1P in combination with chemotherapy. We are also conducting a phase I clinical trial of MORAb-009, a humanized monoclonal antibody targeting mesothelin. Patients with mesothelioma as well as other cancers that express mesothelin are being treated. In addition to utilizing mesothelin as a target for cancer therapy we are evaluating serum mesothelin as a tumor marker for mesothelin expressing tumors. In collaboration with other members of the LMB, as well as Dr. Alan Remaley of the Department of Laboratory Medicine we have developed an ELISA to measure serum mesothelin. Our results show that mesothelin levels are elevated in majority of patients with mesothelioma and ovarian cancer. Our results also show that serum mesothelin levels fall after surgery in patients with peritoneal mesothelioma. These results suggest that serum mesothelin can be a valuable tumor marker to follow and monitor treatment response in patients whose tumors express mesothelin. We will use this ELISA to measure serum mesothelin levels in patients with pleural mesothelioma being treated on a Phase III, randomized, double-blind, placebo-controlled trial of the histone deacetylase inhibitor SAHA. This multi-institutional trial being conducted by Merck Inc. and expected to accrue 660 patients will allow us to determine the utility of mesothelin as a tumor marker in mesothelioma. Serum mesothelin levels will be correlated with tumor stage, tumor burden, and histology as well as response to SAHA.

我们的临床研究重点是靶向治疗表达间皮素的癌症。间皮素是一种40 kda的细胞表面糖蛋白，存在于胸膜、心包和腹膜的正常间皮细胞上。它在间皮瘤、卵巢癌和胰腺癌患者中高度表达。我们正在NCI进行抗间皮素免疫毒素SS1P的临床试验。在I期试验中，我们治疗了34例患者（20例间皮瘤，12例卵巢癌，2例胰腺癌），并注意到一些患者的抗肿瘤活性。基于这些结果，我们即将开始SS1P在间皮瘤患者中的II期临床试验。由于我们的实验室研究显示SS1P与化疗之间存在显著的协同作用，因此本II期研究将评估SS1P与化疗联合的活性。我们也正在进行一项针对间皮素的人源化单克隆抗体MORAb-009的I期临床试验。间皮瘤患者以及其他表达间皮素的癌症患者正在接受治疗。除了利用间皮素作为癌症治疗的靶点外，我们正在评估血清间皮素作为表达间皮素肿瘤的肿瘤标志物。通过与LMB的其他成员以及检验医学系的Alan Remaley博士的合作，我们开发了一种ELISA来测量血清间皮素。我们的研究结果表明，间皮瘤和卵巢癌的大多数患者的间皮素水平升高。我们的研究结果还表明，腹膜间皮瘤患者手术后血清间皮素水平下降。这些结果表明，血清间皮素可以作为一种有价值的肿瘤标志物来跟踪和监测肿瘤中表达间皮素的患者的治疗反应。我们将使用该ELISA检测正在接受组蛋白去乙酰化酶抑制剂SAHA治疗的胸膜间皮瘤患者血清间皮素水平。这项由默克公司（Merck Inc.）开展的多机构试验预计将纳入660名患者，将使我们能够确定间皮素作为间皮瘤肿瘤标志物的效用。血清间皮素水平将与肿瘤分期、肿瘤负荷、组织学以及对SAHA的反应相关。