Moving TIL Therapy Past the Valley of Death

让 TIL 疗法越过死亡之谷

• 批准号: 8338899
• 负责人: John Wilson
• 金额: $ 1.59万
• 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 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8338899
• 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(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性淋巴细胞(TIL)疗法，在这种疗法中，TIL从患者的肿瘤碎片中获得，在体外生长到大量细胞，然后重新注入患者体内(1-4)。问题：尽管它有能力提供完全缓解，但增加治疗性细胞剂量的过程是如此低效和复杂，以至于TIL疗法无法逃脱死亡之谷。建议的解决方案：在之前的第二阶段SBIR GM058978下，我们创造了细胞培养设备技术的范式转变，该技术已被广泛研究用于TIL生产。结果表明，可以创建一种大大简化的流程，使TIL疗法走出死亡之谷，走上商业道路。关键是允许TIL驻留在高透气性、不透液性的薄膜上，该薄膜被淹没在非常规的高水平介质下。我们称这种方法为“霸王龙”。在这种情况下，TIL可以根据需要获得氧气和营养物质，而不需要昂贵而复杂的辅助设备。使用这种设备配置，我们打算将TIL生产过程从多达60个传统设备和30L介质减少到只有2个G-Rex设备和少至4L到5L介质。许多其他生产优势是这种工艺简化所固有的。作为这一计划的结果，应用TIL疗法的盈利潜力将存在，商业实体将被刺激利用TIL疗法的强大结果。调查：我们的研究将通过优化G-REX方案和设备来提供最高效的TIL生产：目标1：确定将TIL快速膨胀过程持续时间降至最低的TIL表面密度目标2：确定在TIL快速膨胀过程(REP)期间将进料频率降至最低的G-REX的最佳高度。目的3：确定全尺寸G-REX装置所允许的透气膜厚度的变化。目的4：优化的G-Rex TIL培养S.O.P.和G-Rex设备规格的全面验证。本方案完成后TIL治疗的现状：与本优化方案分开，处于非优化状态的G-Rex的临床应用已经开始。在这项研究完成后，优化的G-REX将过渡到一项多中心可比性研究，随后是一项随机研究、FDA批准和商业化的TIL疗法。