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

• 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
• 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

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 疾病。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) 个性化、针对患者的产品的要求。在过去的6年里，我们系统地 解决了这些问题：我们简化和完善了我们的制造技术，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 技术人员干预。最后，我们确定了与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 - 特异性T细胞。我们的产品 - Viralym-B - 是一组具有 BK 病毒特异性的 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。我们的 疗法旨在治疗耐药感染/疾病，这种疾病的影响小于 美国有 200,000 人没有标准的护理。因此，在当前 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 干细胞移植受者。此外，我们将进一步降低将该技术转让给私营企业的风险 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。本次申请的成功将奠定 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。