Growth Control in Multiple Myeloma

多发性骨髓瘤的生长控制

基本信息

批准号：
7901331
负责人：
BART BARLOGIE
金额：
$ 85万
依托单位：
UNIV OF ARKANSAS FOR MED SCIS
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-06-05 至 2009-09-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7901331
关键词：
Allogenic Antigens Apoptosis Apoptotic Autologous Autologous Transplantation Biological Biological Availability Biometry Bone Marrow CC-5013 Cells Chromosome abnormality Clinical Clinical Research Clinical Trials Coculture Techniques Collaborations Cytotoxic T-Lymphocytes D Cells Data Detection of Minimal Residual Disease Development Dexamethasone Disease Disease remission Dose Dose-Limiting Drug resistance Epithelial Functional Imaging Funding Gene Expression Profile Gene Expression Profiling Genes Genomic Instability Genotype Growth Heparitin Sulfate Immune Immune response Immunotherapeutic agent In Vitro In complete remission Investigation Light Malignant Neoplasms Malignant neoplasm of testis Melphalan Modeling Molecular Molecular Genetics Monoclonal Antibodies Multiple Myeloma Natural Killer Cells Newly Diagnosed Osteoblasts Osteoclasts Outcome Patients Peptides Property Resistance Scientist Serum Signal Pathway Signal Transduction Source Structure Testing Thalidomide Therapeutic Therapeutic Agents Tissue Banking Tissue Banks Translational Research Treatment Failure Vaccination Velcade Work base cytokine design disease phenotype follow-up high risk improved in vivo novel novel therapeutics outcome forecast patient population prognostic programs response syndecan tumor growth

项目摘要

DESCRIPTION (provided by applicant): Currently in its 10th year of funding, this P01's objective is to achieve durable growth control in multiple myeloma (MM) through highly integrated translational research conducted by clinical and basic scientists. The overall hypothesis will be pursued that various components of the bone marrow microenvironment (ME) contribute to eventual treatment failure by providing (in a MM genotype-specific manner) a plethora of survival and proliferation signals, and that novel therapeutic strategies, coincapacitating MM and ME, will augment growth control. Through a combination of autotransplantsupported high-dose melphalan and therapies that co-target MM and ME, therapeutic strategies will be employed to maximize sustained complete responses. Novel immunotherapeutic approaches are aimed at augmenting autologous host responses via cancer/testis antigen vaccination and employing allogeneic natural killer cells and cytotoxic T lymphocytes. Gene expression profiling (GEP) should improve prognostic models and identify, in concert with Project 4, genes involved in pathogenetic cross talk between MM and ME. Because soluble syndecan-1 has cytokine-trapping properties, studies will determine if blocking heparan sulfate function or its bioavailability may inhibit tumor growth and dissemination. To successfully implement these Projects, 4 Cores are required: A) Admin., Data Mgmt., and Biostatistics; B) Functional Imaging; C) Molecular Genetics; and D) Cell Analysis/Tissue Banking. With access to a large patient population with MM, treated in a hypothesis-driven clinical trial setting with comprehensive follow-up, this P01 will shed light on the molecular and biological mechanisms of disease development/ progression and the current obstacles to sustaining complete remission.

描述（由申请人提供）：目前已进入资助的第 10 个年头，该 P01 的目标是通过临床和基础科学家进行的高度整合的转化研究，实现多发性骨髓瘤 (MM) 的持久生长控制。总体假设是，骨髓微环境 (ME) 的各个组成部分通过提供（以 MM 基因型特异性方式）大量的生存和增殖信号，导致最终的治疗失败，而新的治疗策略，使 MM 和ME，将增强生长控制。通过将自体移植支持的高剂量美法仑与共同靶向 MM 和 ME 的疗法相结合，将采用治疗策略来最大限度地提高持续的完全缓解。新型免疫治疗方法旨在通过癌症/睾丸抗原疫苗接种以及采用同种异体自然杀伤细胞和细胞毒性 T 淋巴细胞来增强自体宿主反应。基因表达谱 (GEP) 应该改进预后模型，并与项目 4 相结合，识别参与 MM 和 ME 之间致病相互作用的基因。由于可溶性 Syndecan-1 具有细胞因子捕获特性，因此研究将确定阻断硫酸乙酰肝素功能或其生物利用度是否可以抑制肿瘤生长和扩散。为了成功实施这些项目，需要 4 个核心：A) 管理、数据管理和生物统计； B) 功能成像； C) 分子遗传学； D) 细胞分析/组织库。通过接触大量 MM 患者群体，并在假设驱动的临床试验环境中进行治疗并进行全面随访，该 P01 将揭示疾病发生/进展的分子和生物学机制以及当前维持完全缓解的障碍。