Overcoming the last barrier to commercialization of virus-specific T cell therapy

克服病毒特异性 T 细胞疗法商业化的最后障碍

• 批准号: 8904289
• 负责人: John Wilson
• 金额: $ 159.96万
• 依托单位: WILSON WOLF MANUFACTURING CORPORATION
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-05 至 2017-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8904289
• 关键词: Adenoviruses; Adverse effects; Allogenic; Cell Culture Techniques; Clinical; Cytomegalovirus; Cytomegalovirus Infections; Data; Devices; Dose; Evaluation; FDA approved; Genetic Engineering; Health; Human Resources; Immune; Immune system; Immunocompromised Host; Infectious Agent; Medical; Medicine; Methods; Paint; Patients; Pharmaceutical Preparations; Phase; Plant Roots; Process; Production; Protocols documentation; Recording of previous events; Safety; Specific qualifier value; Sterility; T cell therapy; T-Lymphocyte; Therapeutic; Touch sensation; Viral; Viral Load result; Virus; Virus Diseases; Wolves; Work; college; commercialization; fighting; follow-up; killings; manufacturing process; member; novel strategies; programs; standard of care; tool

 DESCRIPTION (provided by applicant): T cell therapy for treatment of viral infections in immune compromised patients holds great promise to be a far superior alternative to conventional anti-viral drugs. After years of work, the last remaining barrier is to eliminate genetic engineering that relies on infectious agents when producing the therapeutic T cell doses. These infectious agents create tremendous complexities and are potentially dangerous to patients. This program will overcome that problem and pave the way for the first off-the-shelf virus-specific T cell therapy in history. At the end of this program the optimal manufacturing specifications for virus specific T cell therapy (VST) directed at adenovirus (AdV), BK, and cytomegalovirus (CMV) infections in immune compromised patients. This will serve an unmet medical need, given there are no FDA approved drugs for AdV and BK, and the only FDA approved drug for CMV is highly toxic and often ineffective. Preliminary data paint a compelling picture of how VST can treats the root cause of viral infection; that is the lack of a functional immune system. Data demonstrate VST can restore the immune system's ability to fight viral infection and has minimal side effects. Preliminary data also show how the manufacturing process that creates VST can be greatly simplified with a novel approaches to virus-specific T cell culture. The specific aims follow up on that data. Aim1 Objective: WWM will construct 6-well "G-Rex" T cell culture devices, which will allow comparison of multiple culture conditions in parallel and facilitate the rapid identification of key variables that support optimal VST production. Aim 1 Deliverable: We will have fully functional, sterile, 6-well G-Rex devices for the VST optimization studies outlined in Aim 2. The construction of this cell culture tool will allow or collaborators from Baylor College of Medicine to rapidly and efficiently assess multiple conditions in parallel. Aim 2 Objective: Find the optimal stimulation protocol to maximize the purity and killing capacity of a therapeutic VST dose. Aim 2 Deliverable: Optimized virus-specific T cell stimulation protocols that maximize purity and killing capacity will be available for evaluation at full scale in Aim 4. Aim 3 Objective: Use the data of Aim 2 to create G-Rex devices of optimal size for use in the verification study of Aim 4. Aim 3 Deliverable: Full scale G-Rex devices will be available for use in Aim 4. Aim 4 Objective: Verify protocols optimized in Aim 2 are repeatable in full scale G-Rex devices. Aim 4 Deliverable: Specifications defining the most efficient manufacturing conditions for maximum VST killing capacity within alloreactivity acceptance criteria, without the need for infectious agents in the manufacturing process, will be available for use in Phase IIb.

 描述（由适用提供）：用于治疗免疫药物损害患者病毒感染的T细胞疗法具有很大的保证，它是传统抗病毒药物的替代品。经过多年的工作，最后剩下的障碍是消除产生治疗性T细胞剂量时依赖感染剂的基因工程。这些感染力会产生巨大的复杂性，对患者有潜在的危险。该计划将克服该问题，并为历史上第一种现成的特定T细胞疗法铺平道路。在该计划的末尾，针对腺病毒（ADV），BK和巨细胞病毒（CMV）感染的病毒特异性T细胞疗法（VST）的最佳制造规格（VST）。鉴于没有FDA批准的ADV和BK的药物，这将满足未满足的医疗需求，并且唯一获得FDA批准的CMV药物是有毒的，而且常常无效。初步数据描绘了VST如何处理病毒感染的根本原因的令人信服的图片；这就是缺乏功能性免疫系统。数据表明，VST可以恢复免疫系统对抗病毒感染的能力，并具有最小的副作用。初步数据还显示了如何通过新颖的病毒特异性T细胞培养方法来大大简化创建VST的制造过程。该数据的具体目的跟进。 AIM1目标：WWM将构建6孔“ G-Rex” T细胞培养设备，这将允许并行比较多种培养条件，并促进对支持最佳VST生产的关键变量的快速识别。 AIM 1可交付：我们将拥有功能齐全的，无菌的6孔G-Rex设备 VST优化研究在AIM 2中概述了。该细胞培养工具的构建将允许贝勒医学院的合作者和合作者同时快速有效地评估多个条件。目标2目标：找到最佳的刺激方案，以最大程度地提高治疗性VST剂量的纯度和杀伤能力。 AIM 2可交付：AIM 4目标：AIM 3目标：使用AIM 2的数据来创建最佳尺寸的G-Rex设备，以在AIM 4的验证研究中使用AIM 4的AIM 4。AIM 3可交付：全尺度G-Rex设备可在AIM中使用AIM 4 AEX 4目标，AIM 4目标可用：AIM 4。 G-Rex设备。 AIM 4可交付：定义最大效率的制造条件的规格，以在同种异体反应性接受标准内最大的VST杀戮能力，而无需在制造过程中使用传染性药物，可用于IIB期。