Development of a new drug for treating autoimmune uveitis

治疗自身免疫性葡萄膜炎新药的研制

基本信息

批准号：
10321980
负责人：
FENG C LIN
金额：
$ 25.54万
依托单位：
ABCON THERAPEUTICS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10321980
关键词：
Active Immunization Adoptive Transfer Affinity Animal Model Animals Antibody-drug conjugates Antigens Apoptosis Arrestins Autoimmune Diseases B-Lymphocytes Binding Biological Assay Biotechnology Blindness CD6 antigen Cell Line Cell Surface Proteins Cell surface Cells Cleaved cell Clinic Clinical Clinical Trials Development Disease Drug Targeting Experimental Models Eye FDA approved Human Imaging Techniques Immunoglobulin G In Vitro Inflammation Lasers Lead Lysosomes Mediating Mitosis Mitotic Modeling Monitor Monoclonal Antibodies Mus Ophthalmoscopy Optical Coherence Tomography Organ Pathogenicity Patients Pharmaceutical Preparations Phase Physiological Pilot Projects Proliferating Proteins Raji Cell Retina Scanning Stains T-Lymphocyte Technology Therapeutic Time Tissues Toxic effect Toxin Toxin Conjugates Treatment Efficacy Tubulin Uveitis antigen-specific T cells autoimmune uveitis autoreactive T cell cancer therapy clinical development cytotoxicity design drug candidate efficacy testing experimental study humanized mouse in vivo neoplastic cell novel novel therapeutics ocular imaging phase 2 study polymerization retinal damage side effect therapeutic development

项目摘要

Summary Autoimmune uveitis is a major cause of blindness in which retinal antigen-specific T cells lead to ocular inflammation and vision loss. Similar to the treatment of other T cell-mediated autoimmune diseases, selective suppression of the pathogenic T cells is the “holy grail” of therapeutic development. In pilot studies, we have developed a novel antibody-drug conjugate (ADC) with combined T cell targeting and potent anti-mitosis activity, which is designed to selectively kill the proliferating autoreactive T cells while sparing the other cells including normal T cells. In this Phase I application, we will first demonstrate that this ADC selectively kills proliferating uveitogenic T cells while sparing normal T cells and other cells both in vitro and in vivo, then determine its in vivo treatment efficacy and potential off-target effects in two animal models of autoimmune uveitis. These studies will provide the required proof-of-concept for a Phase II development of this promising ADC towards IND-enabling studies and further clinical development.

概括自身免疫性葡萄膜炎是导致失明的主要原因，其中视网膜抗原特异性 T 细胞导致眼部炎症和视力丧失，与其他 T 细胞介导的治疗类似。自身免疫性疾病，选择性抑制致病性T细胞是治疗的“圣杯” 在试点研究中，我们开发了一种新型抗体-药物缀合物。 (ADC) 具有组合 T 细胞靶向和有效的抗有丝分裂活性，旨在选择性杀死增殖的自身反应性 T 细胞，同时保留其他细胞，包括正常细胞在此一期应用中，我们将首先证明该 ADC 选择性杀死 T 细胞。在体外和体内增殖葡萄膜原性 T 细胞，同时保留正常 T 细胞和其他细胞体内，然后确定其在两只动物中的体内治疗效果和潜在的脱靶效应这些研究将为自身免疫性葡萄膜炎模型提供所需的概念验证。这种有前途的 ADC 的 II 期开发旨在支持 IND 研究和进一步临床发展。