Development of anti-human TL1A monoclonal antibody for the treatment of human ast

开发用于治疗人类AST的抗人TL1A单克隆抗体

• 批准号: 7805392
• 负责人: Vadim V Deyev
• 金额: $ 30万
• 依托单位: NIGHTHAWK BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-15 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7805392
• 关键词: Accident and Emergency department; Accounting; Acute; Address; Admission activity; Affect; Allergic; Animal Model; Antibodies; Asthma; Autoimmune Process; Blocking Antibodies; Breathing; Bronchodilator Agents; Cellular Assay; Cessation of life; Characteristics; Chest; Child; Chronic; Coughing; Data; Developed Countries; Development; Disease; Effectiveness; Evaluation; Event; Expenditure; Family; Goals; Government; Grant; Healthcare; Healthcare Systems; Heating; Hospitalization; Hospitals; Human; Hybridomas; Immune; Immune system; Incidence; Inflammation; Inflammatory; Inflammatory Response; Laboratories; Lead; Life; Ligands; Lung; Lung Inflammation; Lung diseases; Maintenance; Mediating; Medical; Modality; Modeling; Monkeys; Monoclonal Antibodies; Mucous body substance; Mus; Ovalbumin; Pathogenesis; Patients; Phase; Pilot Projects; Pneumonia; Positioning Attribute; Prevalence; Primates; Production; Publishing; Quality of life; Regulatory T-Lymphocyte; Research; Safety; Scientist; Shortness of Breath; Signal Transduction; Sputum; Staging; Symptoms; System; T-Lymphocyte; TNFSF15 gene; Technology; Testing; Therapeutic; Therapeutic Monoclonal Antibodies; Therapeutic antibodies; Transgenic Organisms; United States; Wheezing; Work; cost; cytokine; disorder control; effective therapy; experience; humanized antibody; improved; in vivo; inner city; mouse model; nonhuman primate; novel; novel strategies; novel therapeutics; preclinical safety; prevent; public health relevance; repaired; research and development; response; safety study

DESCRIPTION (provided by applicant): Asthma is a chronic, debilitating disease characterized by intermittent attacks of wheezing, shortness of breath, chest tightness, cough and excess sputum/mucus production. As many as 300 million people worldwide may have some form of asthma and the prevalence has steadily increased at an alarming rate over the past two decades. Today in the United States alone, more than 24 million people (~ 10 million children) have asthma resulting in more than 500,000 hospital admissions annually due to asthmatic symptoms and more than 5000 deaths each year. Most asthmatics have a mild form of the disease, which is well controlled by inhaled bronchodilators; however, up to 5% have severe asthma for which there is no effective treatment. These are the patients who show up at the emergency room during an acute, life threatening attack and can remain in the hospital for up to one week or longer. The cost of asthma is great and asthma-related hospitalizations accounts for almost 80% of the healthcare expenditures for this disease representing a huge financial burden on both families and governments. The cost of asthma in the United States is estimated to be more than $14 billion per year. The Heat Biologics R&D team is developing a novel treatment that deals directly with the underlying causes of asthma, rather than just symptom relief, and if successful, will revolutionize the way asthma is treated. Controlling inflammation is now a central objective of asthma therapy and is essential for better control of the disease. Asthma is an immune-mediate disease and, therefore, new, more effective treatments will modulate the immune system to block the onset and progression of asthma. Heat Biologic's novel approach is focused on modulating T cell activity and pro-inflammatory cytokine production and secretion such that the immune system, which is overactive in diseases like asthma, is 'dialed down' to a level where there is no longer chronic inflammation present in the lungs and the airways are allowed to repair and return to normal function. The specific aims for this grant are to 1) generate and characterize a humanized form of the current molecule that would be appropriate for eventual testing in human asthmatics and 2) to continue to evaluate the effectiveness of this molecule as a novel treatment for the 'causal events of asthma' in well characterized animal models. The work conducted in Phase 1 of this grant will enable Heat Biologics to be in a position to initiate production of high quality material for use in preclinical safety studies in depth analysis if the mechanism of action and to demonstrate the potential therapeutic benefits to human asthmatics. PUBLIC HEALTH RELEVANCE: As many as 300 million people worldwide may have some form of asthma and both the incidence and prevalence are increasing at an alarming rate. Today in the United States alone, more than 24 million people (~ 10 million children) have asthma resulting in more than 500,000 hospitalizations annually due to asthmatic symptoms, a huge drain on healthcare system and more than 5000 deaths each year (approximately 450 deaths per month, 100 per week and 15 each day!). The overall goal of this project is to develop and validate a novel therapeutic for the treatment of asthma that addresses the underlying causal factors of the disease, not just treating symptoms, providing a means for improving the quality of life for the millions who suffer from asthma.

描述（由申请人提供）：哮喘是一种慢性，令人衰弱的疾病，其特征是喘息，呼吸急促，胸部紧绷，咳嗽和过量的痰/粘液/粘液产生。在过去的二十年中，全球多达3亿人可能有某种形式的哮喘，并且患病率稳步上升。仅今天，仅在美国，由于哮喘症状和每年有5000多人死亡，每年有超过2400万人（约1000万儿童）患哮喘每年有500,000多人入院。 大多数哮喘患者都有一种温和的疾病形式，由吸入支气管扩张剂很好地控制。但是，多达5％的人患有严重的哮喘，没有有效的治疗方法。这些患者在急性期间出现在急诊室，威胁生命的攻击，可以在医院呆一周或更长时间。哮喘的成本很大，与哮喘相关的住院率占该疾病的医疗支出的80％，代表了家庭和政府的巨大经济负担。美国哮喘的成本估计每年超过140亿美元。热生物制剂团队正在开发一种新颖的治疗方法，直接处理哮喘的根本原因，而不仅仅是症状缓解，如果成功的话，将彻底改变对哮喘的治疗方式。 控制炎症现在是哮喘治疗的核心目标，对于更好地控制该疾病至关重要。哮喘是一种免疫疾病，因此，新的，更有效的治疗方法将调节免疫系统以阻止哮喘的发作和进展。 Heat Biologic的新方法的重点是调节T细胞活性和促炎性细胞因子的产生和分泌，因此，在诸如哮喘之类的疾病中过度活跃的免疫系统被“拨打”到不再存在肺部且气道中的慢性炎症的水平，并且允许空气恢复正常功能。该赠款的具体目的是1）生成和表征当前分子的人性化形式，该形式适合于人类哮喘患者最终测试，而2）继续评估该分子作为对特征性动物模型中哮喘的哮喘的因果事件的一种新颖处理。如果作用机理并证明对人类哮喘患者的潜在治疗益处，则在本赠款第1阶段进行的工作将使热生物制剂能够启动高质量材料的生产，以在临床前安全研究中使用。 公共卫生相关性：全球多达3亿人可能有某种形式的哮喘，并且发病率和流行率都以惊人的速度增加。仅今天，仅在美国，由于哮喘症状，医疗系统的巨大耗竭和每年的5000多人死亡（每月约450人死亡，每周100人，每周100例，每周15例和每天15人！），仅在美国，每年有超过2400万人（约1000万儿童）每年有500,000多人住院。该项目的总体目标是开发和验证一种用于治疗哮喘的新型治疗方法，该治疗涉及该疾病的根本因素，而不仅仅是治疗症状，从而为改善哮喘患者的生活质量提供了一种手段。