Intra-salivary gland autotransplantation of marrow mesenchymal stromal cells for treatment of radiation induced xerostomia

唾液腺内自体骨髓间充质干细胞移植治疗放射引起的口干症

• 批准号: 10793666
• 负责人: RANDALL J KIMPLE
• 金额: $ 60.48万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10793666
• 关键词: Intra; salivary; gland; autotransplantation; marrow

Project Abstract Dry mouth is a significant side-effect of radiation therapy for head and neck cancer patients. Several factors contribute to dry mouth. Decreased production of saliva is called hyposalivation. Poor quality and function of saliva is called salivary dysfunction. Together, these cause xerostomia, or what a patient experiences as simply dry mouth. Xerostomia can lead to tooth decay, infections, difficulty speaking, impaired swallowing, poor nutrition, and has a significant negative effect on quality of life. Doctors recommend that patients suck on hard candy, chew gum, use saliva substitutes, and/or carry a water bottle with them at all times. None of these are particularly effective. Our long-term goal is to improve outcomes for patients suffering from radiation-induced dry mouth. We seek to achieve this goal by providing convincing evidence that innovative cellular therapies can safely and significantly improve salivary gland function and quality of life. The team of investigators tackling this project is uniquely suited to complete the work. Success would lead directly to the next phase of clinical testing. We have expertise in caring for head and neck cancer patients, developing bone marrow derived mesenchymal stromal cells (MSCs) as cellular therapies, and studying salivary function. The overall objective of this application is to perform a Phase 1 trial to test the safety and tolerability of IFN-g pre-licensed MSCs for treatment of radiation-induced xerostomia in head and neck cancer patients. To achieve our goals, we propose two aims spread across the two phases of this application. In Aim 1, we will work closely with the NIH, NIDCR, and FDA to complete all necessary milestones to activate the proposed clinical trial (Aim 1) and enroll our first patient (UG3 phase). In Aim 2, we will perform a Phase 1 safety and tolerability study of IFN-g pre-licensed autologous MSCs in patients with radiation-induced xerostomia in order to define the recommended phase 2 dose (UH3 phase). An expansion cohort at the recommended phase 2 dose (n=12 additional patients) will be included in order to confirm the safety profile, better describe the toxicity, and investigate the efficacy of MSC injection to treat radiation-induced xerostomia. We will assess the efficacy using both validated patient-reported outcome measures and through assessment of salivary production and composition. This trial is expected to provide key data used to design the next clinical trial. A phase 2 study would further test the efficacy of MSCs in head and neck cancer patients. These studies will also provide important data to support future grant applications aimed at improving the salivary response through ex vivo engineering of MSCs.

项目摘要 口干是头颈部癌症患者放射治疗的一个重要副作用。几个因素 有助于口干。唾液分泌减少称为唾液过少。质量和功能差 唾液被称为唾液功能障碍。这些因素共同导致口腔干燥症，或者说， 口干。口腔干燥症会导致蛀牙、感染、说话困难、吞咽障碍、 营养不良，并对生活质量产生重大负面影响。医生建议病人用力吮吸 糖果，口香糖，使用唾液替代品，和/或随身携带水瓶。这些都不是 特别有效。我们的长期目标是改善放射性干细胞患者的预后， 嘴里我们寻求通过提供令人信服的证据来实现这一目标，即创新的细胞疗法可以 安全并显著改善唾液腺功能和生活质量。处理这一问题的调查小组 该项目是唯一适合完成这项工作。成功将直接导致下一阶段的临床试验。 我们在头颈部癌症患者的护理方面拥有专业知识， 基质细胞（MSC）作为细胞疗法，并研究唾液功能。本申请的总体目标 进行1期试验，以测试IFN-g预许可的MSC治疗以下疾病的安全性和耐受性： 头颈部癌症患者的放射性口腔干燥症。 为了实现我们的目标，我们提出了两个目标，分布在这个应用程序的两个阶段。在目标1中，我们 与NIH、NIDCR和FDA密切合作，完成所有必要的里程碑，以启动拟议的 临床试验（Aim 1）并招募我们的第一名患者（UG 3期）。在目标2中，我们将进行1期安全性研究， IFN-g预许可的自体MSC在放射性口干患者中的耐受性研究 确定推荐的II期剂量（UH 3期）。推荐II期剂量的扩展队列 （n=12例额外患者）将被纳入，以确认安全性特征，更好地描述毒性， 探讨MSC注射治疗放射性口干症的疗效。我们将使用 既验证了患者报告的结局指标，又通过评估唾液分泌， 混合物.预计该试验将提供用于设计下一项临床试验的关键数据。一项2期研究 将进一步测试MSC在头颈癌患者中的功效。这些研究还将提供 重要的数据，以支持未来的赠款申请，旨在改善唾液的反应，通过离体 MSC的工程化。