Moving TIL Therapy Past the Valley of Death

让 TIL 疗法越过死亡之谷

• 批准号: 8541795
• 负责人: John Wilson
• 金额: $ 61.16万
• 依托单位: WILSON WOLF MANUFACTURING CORPORATION
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-26 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8541795
• 关键词: Area; Automobile Driving; Back; Cell Culture Techniques; Cells; Cessation of life; Devices; Disease remission; Dose; Equipment; Frequencies; Gases; Head; Height; In Vitro; Investigation; Liquid substance; Membrane; Metastatic Melanoma; Nutrient; Outcome; Oxygen; Patients; Phase; Positioning Attribute; Private Sector; Process; Production; Protocols documentation; Randomized; Small Business Innovation Research Grant; Solutions; Specific qualifier value; Surface; Technology; Therapeutic; Thick; Tumor-Infiltrating Lymphocytes; Validation; abstracting; clinical application; commercialization; cost effective; density; effective therapy; feeding; operation; programs; tumor; tumor infiltrating lymphocyte therapy

DESCRIPTION (provided by applicant): The Field: The most effective treatment for metastatic melanoma is Tumor Infiltrating Lymphocyte (TIL) therapy, in which TILs are obtained from a patient's tumor fragments, grown to an immense quantity in vitro, and infused back into the patient (1-4). The Problem: Despite its ability to provide complete remission, the process of growing a therapeutic cell dose is so inefficient and complicated that TIL therapy cannot escape the Valley of Death. The Proposed Solution: Under prior Phase II SBIR GM058978, we created a paradigm shift in cell culture device technology that has been extensively studied for TIL production. The results demonstrate a greatly simplified process can be created that will allow TIL therapy to move beyond the Valley of Death and onto a commercial path. The key is to allow TILs to reside on a highly gas permeable, liquid impermeable membrane submerged under an unconventionally high level of medium. We call this approach "G-Rex". With TILs in this position, they have access to oxygen and nutrients on demand without need of expensive and complicated ancillary equipment. Using this device configuration, we intend to reduce the TIL production process from up to 60 conventional devices and 30L of medium to just 2 G-Rex devices and as little as 4L to 5L of medium. Many other production advantages are inherent to this level of process simplification. As a result of this program, the potential for profit by applying TIL therapy will exist and commercial entities will be spurred to capitalize on the powerful outcomes of TIL therapy. The Investigation: Our investigation will provide the most efficient TIL production possible by optimizing G- Rex Protocols and devices: Aim 1: Determine the optimal TIL surface density that minimizes the duration of TIL Rapid Expansion Process Aim 2: Determine the optimal height of the G-Rex that will minimize the feeding frequency during the TIL Rapid Expansion Process (REP). Aim 3: Define the variance of gas permeable membrane thickness allowed in full scale G-Rex devices. Aim 4: Full scale validation of optimized G-Rex TIL culture S.O.P.s and G-Rex device specifications. The status of TIL therapy upon completion of this program: Separate from this optimization program, clinical application of G-Rex in the non-optimized state is already occurring. Upon completion of this investigation, the optimized G-Rex will transition into a multi-center comparability study followed by a randomized study, FDA approval, and commercially available TIL therapy.

描述（由申请人提供）：领域：转移性黑色素瘤最有效的治疗方法是肿瘤浸润淋巴细胞（TIL）治疗，其中从患者的肿瘤碎片中获得TIL，体外生长至大量，并注入患者（1-4）。问题：尽管能够提供完全缓解的能力，但增加治疗性细胞剂量的过程效率低下且复杂，以至于TIL治疗无法逃脱死亡山谷。提出的解决方案：在先前的II期SBIR GM058978下，我们创建了细胞培养设备技术的范式转移，该技术已被广泛研究以用于TIL生产。结果表明，可以创建一个极大的简化过程，这将使直到治疗超越死亡山谷并进入商业路径。关键是让TIL驻留在高度可渗透的液体不渗透的膜上，在非常规高水平的培养基下淹没。我们称这种方法为“ G-Rex”。在此位置，他们可以按需使用氧气和养分，而无需昂贵且复杂的辅助设备。使用此设备配置，我们打算将TIL生产过程从60个常规设备和30升介质减少到只有2个G-Rex设备，而介质则仅为4L至5L介质。许多其他生产优势是该过程简化级别固有的。该计划的结果是，通过应用直到治疗的利润潜力将存在，商业实体将被刺激利用TIL治疗的强大结果。调查：我们的研究将通过优化G-REX方案和设备来提供最有效的TIL生产：目标1：确定最佳的TIL表面密度，以最大程度地减少TIL快速扩张过程目标目标2：确定G-Rex的最佳高度，该高度将在TIL快速扩张过程中最小化饲料频率（REP）。 AIM 3：定义全尺度G-Rex设备中允许的气体渗透膜厚度的方差。目标4：对优化的G-Rex TIL培养S.O.P.S和G-Rex设备规范的全面验证。该计划完成后TIL治疗的状态：与该优化计划分开，G-Rex在非优化状态中的临床应用已经存在。在完成这项研究后，优化的G-Rex将过渡到多中心的可比性研究，然后进行随机研究，FDA批准和市售的TIL治疗。