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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.

摘要自身免疫性葡萄膜炎是致盲的主要原因，视网膜抗原特异性T细胞导致眼部发炎和视力丧失。类似于其他T细胞介导的治疗自身免疫性疾病中，选择性抑制致病T细胞是治疗的“圣杯” 治疗方面的发展。在初步研究中，我们开发了一种新的抗体-药物结合物 (ADC)结合T细胞靶向和强大的抗有丝分裂活性，旨在选择性地杀死增殖中的自身反应性T细胞，而保留包括正常在内的其他细胞 T细胞。在此阶段I应用程序中，我们将首先演示该ADC选择性地杀死在体外和体外扩增葡萄膜生成T细胞，同时保留正常T细胞和其他细胞然后在两个动物身上确定其体内治疗效果和潜在的靶外效应自身免疫性葡萄膜炎模型。这些研究将提供所需的概念验证这一前景看好的ADC的第二阶段开发将使IND研究和进一步的临床发展。