Path to Commercialization of the first “off the shelf” T cell product

第一个“现成”T 细胞产品的商业化之路

基本信息

批准号：
9301696
负责人：
ADRIAN Philip GEE
金额：
$ 98.87万
依托单位：
VIRACYTE, LLC
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-06-15 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9301696
关键词：
Accelerometer Address Adoptive Transfer Adverse effects Allogenic Alternative Therapies Antiviral Agents B-Lymphocytes BK Virus Biological Biological Assay Blood Cell Count Cell Culture Techniques Cell Line Cells Child Cidofovir Clinical Collaborations Communities Contracts Cystitis Data Devices Disease Dose Drug resistance Drug usage Encephalitis Epitopes Feces Foundations Funding Gases Goals Grant Hematopoietic Stem Cell Transplantation Hemorrhage Immune Immunocompromised Host In Vitro Individual Infection Infusion procedures Institutional Review Boards Interferons Intervention Kidney Diseases Lead Length of Stay Lymphocyte Measures Medicine Monitor Morbidity - disease rate National Heart, Lung, and Blood Institute Nephritis Output Patients Permeability Persons Phase Phase II Clinical Trials Preparation Private Sector Product Approvals Production Protocols documentation Public Domains Refractory Reporting Resistance Resolution Risk Safety Scientist Signs and Symptoms Specificity Staining method Stains Syndrome System T cell therapy T-Lymphocyte Technology Technology Transfer Testing Therapeutic Time Toxic effect Transplant Recipients Treatment Efficacy United States United States National Institutes of Health Urine Viral Viral Load result Viral Physiology Virus Virus Diseases Work base cell bank clinical investigation college commercialization cost cytokine cytotoxic deep sequencing in vivo manufacturing process manufacturing scale-up phase I trial prospective response safety testing scale up standard of care success symptomatic improvement

项目摘要

ABSTRACT The adoptive transfer of virus-specific T cells has produced remarkable clinical results in patients with viral disease. However, broader implementation of this therapy has been limited by the (i) prohibitive production costs, (ii) complexity of manufacture, (iii) prolonged time for preparation and product release, and (iv) the requirement for individualized, patient-specific products. Over the past 6 years we have systematically addressed these problems: we simplified and refined our manufacturing technology, removed biohazardous components and employed a new cell expansion platform using a gas permeable culture device which promotes the proliferation and survival of large cell numbers in a GMP-compliant closed system with minimal technician intervention. Finally, we have established the clinical benefit associated with the infusion of partially HLA matched virus-specific T cells that are prospectively generated and banked, making them available for immediate “off the shelf” use. Thus, with the purpose of moving beyond highly specialized academic centers we established a Baylor College of Medicine-affiliated company called ViraCyte with the goal of commercializing “off the shelf” virus- specific T cells. Our product - Viralym-B - is a bank of T cell lines with specificity for BK virus, which, in immunocompromised individuals including children, is responsible for severe clinical syndromes like hemorragic cystitis and nephropathy that can lead to significant morbidity and prolonged hospital stay. Our therapy is intended for the treatment of drug-resistant infections/disease, a condition that afflicts less than 200,000 persons in the United States and for which there is no standard of care. Thus, in the current application we will test the safety and potential for anti-viral activity of Viralym-B in allogeneic hematopoietic stem cell transplant recipients. In addition, we will further de-risk the transfer of this technology to a private sector contract manufacturing organization (CMO) by transitioning our cell production from an open to an entirely closed system and validating our scale-up manufacture protocol. Success of this application will lay the foundation for a Phase IIb study to confirm the efficacy of “off the shelf” Viralym-B cells and facilitate market approval, thereby moving T cell therapy for BK virus into the public domain as a standard of care.

抽象的病毒特异性T细胞的过继转移在病毒患者中产生了显着的临床效果然而，这种疗法的更广泛实施受到以下因素的限制：(i) 禁止生产。成本，(ii) 制造的复杂性，(iii) 制备和产品发布的时间较长，以及 (iv) 在过去的 6 年里，我们系统地满足了个性化、针对患者的产品的需求。解决了这些问题：我们改进了制造技术，消除了生物危害组件并采用了一种新的细胞扩增平台，该平台使用透气培养装置，在符合 GMP 的封闭系统中以最小的量促进大量细胞的增殖和存活最后，我们确定了部分输注相关的临床益处。预期生成并储存的 HLA 匹配病毒特异性 T 细胞，使其可用于立即“现成”使用。因此，为了超越高度专业化的学术中心，我们建立了贝勒医学院附属公司 ViraCyte 的目标是将“现成”病毒商业化 - 我们的产品 - Viralym-B - 是一组对 BK 病毒具有特异性的 T 细胞系，其中免疫功能低下的个体，包括儿童，是导致严重临床综合征的原因，例如出血性膀胱炎和肾病可能导致严重的发病率和住院时间延长。疗法旨在治疗耐药感染/疾病，这种疾病影响的程度小于美国有 200,000 人，目前没有标准的护理。我们将测试 Viralym-B 在同种异体造血中的安全性和抗病毒活性潜力此外，我们将进一步降低将该技术转让给私人的风险。部门合同制造组织 (CMO)，将我们的电池生产从开放式转变为开放式完全封闭的系统并验证我们的放大生产协议将奠定基础。为 IIb 期研究奠定基础，以确认“现成”Viralym-B 细胞的功效并促进市场发展批准，从而将 BK 病毒的 T 细胞疗法作为护理标准进入公共领域。