口干症是放射治疗头颈恶性肿瘤患者的一个重要副作用。初步数据表明，间质干/干细胞（MSCs）可以改善唾液功能。我们进行了一项首个人体试验，研究了干扰素γ（IFNγ）刺激的自体骨髓源MSCs（MSC(M)）对放射诱导的口干症（RIX）的治疗。我们在这里提供初级安全性和次级疗效终点结果。 我们进行了一项单中心初步临床试验，研究了自体IFNγ刺激的MSC(M)的安全性和耐受性。该研究在经批准的食品药品监督管理局调查新药申请下进行，使用经机构审查委员会批准的方案（NCT04489732）。患者接受髂脊骨髓穿刺，并分离、培养、刺激IFNγ并冷冻保存MSC(M)以备后续使用。冷冻保存的细胞在解冻后在培养基中恢复，然后患者在超声引导下接受10 × 106个MSC(M)的单次注射到右侧颌下腺。主要目标是通过评估剂量限制性毒性（DLT）来确定安全性和耐受性。DLT被定义为标准10分疼痛评分中颌下腺疼痛>5或注射后1个月内的任何严重不良事件（SAE）。次级目标包括通过唾液量化和使用三个经验证的生活质量工具进行疗效分析。定量结果以均值和标准偏差报告。 6名已于至少2年前（平均7.8年前）完成放射治疗的放射诱导性口干症患者纳入了该初步研究。中位年龄为71岁（61-74岁）。5名（83%）患者为男性。5名患者（83%）接受了放化疗，1名患者（17%）接受了单纯放疗。颌下腺注射后，50%的患者出现了一级疼痛，所有疼痛在4天内缓解。无患者报告注射后1个月的疼痛，注射后1个月内未报告SAE或其他DLTs。次级终点分析显示唾液产生有增加的趋势。在MSC(M)注射后的1个月和3个月，3名患者（50%）的非刺激唾液有所增加。生活质量调查也显示有改善的趋势。 在RIX患者的单侧颌下腺注射自体IFNγ刺激的MSC(M) 在此初步研究中安全且耐受。在次级终点中观察到唾液的数量和生活质量有所改善的趋势。这项首次人体研究支持进一步探究在RIX治疗和改善头颈恶性肿瘤患者生活质量方面，以IFNγ刺激的MSC(M)同时注射到颌下腺的创新方法。 版权所有 © 2023 国际细胞与基因治疗学会。由Elsevier Inc.出版。保留所有权利。

Xerostomia, or the feeling of dry mouth, is a significant side effect of radiation therapy for patients with head and neck cancer (HNC). Preliminary data suggest that mesenchymal stromal/stem cells (MSCs) can improve salivary function. We performed a first-in-human pilot study of interferon gamma (IFNγ)-stimulated autologous bone marrow-derived MSCs, or MSC(M), for the treatment of radiation-induced xerostomia (RIX). Here we present the primary safety and secondary efficacy endpoints.A single-center pilot clinical trial was conducted investigating the safety and tolerability of autologous IFNγ-stimulated MSC(M). The study was conducted under an approved Food and Drug Administration Investigational New Drug application using an institutional review board-approved protocol (NCT04489732). Patients underwent iliac crest bone marrow aspirate and MSC(M) were isolated, cultured, stimulated with IFNγ and cryopreserved for later use. Banked cells were thawed and allowed to recover in culture before patients received a single injection of 10 × 106 MSC(M) into the right submandibular gland under ultrasound guidance. The primary objective was determination of safety and tolerability by evaluating dose-limiting toxicity (DLT). A DLT was defined as submandibular pain >5 on a standard 10-point pain scale or any serious adverse event (SAE) within 1 month after injection. Secondary objectives included analysis of efficacy as measured by salivary quantification and using three validated quality of life instruments. Quantitative results are reported as mean and standard deviation.Six patients with radiation-induced xerostomia who had completed radiation at least 2 years previously (average 7.8 years previously) were enrolled in the pilot study. The median age was 71 (61-74) years. Five (83%) patients were male. Five patients (83%) were treated with chemoradiation and one patient (17%) with radiation alone. Grade 1 pain was seen in 50% of patients after submandibular gland injection; all pain resolved within 4 days. No patients reported pain 1 month after injection, with no SAE or other DLTs reported 1 month after injection. The analysis of secondary endpoints demonstrated a trend of increased salivary production. Three patients (50%) had an increase in unstimulated saliva at 1 and 3 months after MSC(M) injection. Quality of life surveys also showed a trend toward improvement.Injection of autologous IFNγ-stimulated MSC(M) into a singular submandibular gland of patients with RIX is safe and well tolerated in this pilot study. A trend toward an improvement in secondary endpoints of salivary quantity and quality of life was observed. This first-in-human study provides support for further investigation into IFNγ-stimulated MSC(M) injected in both submandibular glands as an innovative approach to treat RIX and improve quality of life for patients with HNC.Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.