Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia)
Phase 1 clinical study of cell therapy with effective-mononuclear cells (E-MNC) for radiogenic xerostomia (first-in-human study) (FIH study on E-MNC therapy for radiogenic xerostomia)
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DOI：
10.1097/md.0000000000020788
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发表时间：
2020-06-01
期刊：
影响因子：
1.6
通讯作者：
Asahina, Izumi
中科院分区：
文献类型：
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作者：
Sumita, Yoshinori;Iwamoto, Naoki;Asahina, Izumi
背景：大多数头颈癌患者的治疗包括电离辐射加或不加化疗。这种治疗对照射野中的唾液腺造成不可逆的损伤，伴随着分泌液体的腺泡细胞的损失和唾液分泌的显著减少。目前没有足够的常规治疗这种情况。近年来，我们开发了一种有效的培养方法来提高外周血单个核细胞（PBMNC）的抗炎和血管生成表型，这种有效的条件化PBMNC（E-MNC）治疗在临床前研究中显示出有希望的改善放射损伤唾液腺的功能。然而，E-NMC治疗的安全性和效果尚未在人体中进行评估。这项正在进行的首次人体研究的目的是评估E-MNC治疗放射性口干症的安全性、耐受性和部分疗效。方法/设计：这项I期首次人体研究是一项开放标签、单中心、两步剂量递增研究。总共6名放射治疗后5年以上没有头颈癌复发并患有放射诱导的口干症的患者将接受来自自体PBMC的E-NMCs移植到下颌下腺。干预持续时间为1年。为了分析唾液分泌的恢复情况，将进行牙龈测试。为了分析萎缩唾液腺的恢复情况，将进行唾液腺的计算机断层扫描（CT）和磁共振成像（MRI）。主要终点是方案的安全性。次要终点为全唾液分泌和唾液腺萎缩较基线的变化。讨论：这将是第一个使用E-MNCs对严重辐射诱导的口干症患者进行再生治疗的临床研究。本研究的结果有望为放射性口干症的低侵袭性细胞治疗的发展做出贡献。
Background: Treatment for most patients with head and neck cancers includes ionizing radiation with or without chemotherapy. This treatment causes irreversible damage to salivary glands in the irradiation field accompanied by a loss of fluid-secreting acinar cells and a considerable decrease of saliva secretion. There is currently no adequate conventional treatment for this condition. In recent years, we developed an effective culture method to enhance the anti-inflammatory and vasculogenic phenotypes of peripheral blood mononuclear cells (PBMNCs), and such effectively conditioned PBMNC (E-MNC) therapy has shown promising improvements to the function of radiation-injured salivary glands in preclinical studies. However, the safety and effect of E-NMC therapy have yet assessed in human. The objective of this ongoing first-in-man study is to assess the safety, tolerability, and in part the efficacy of E-MNC therapy for treating radiation-induced xerostomia. Methods/design: This phase 1 first-in-man study is an open-label, single-center, two-step dose escalation study. A total of 6 patients, who had no recurrence of head and neck cancer over 5 years following radiation therapy and suffered from radiation-induced xerostomia, will receive a transplantation of E-NMCs derived from autologous PBMNCs to a submandibular gland. The duration of the intervention will be 1 year. To analyze the recovery of salivary secretion, a gum test will be performed. To analyze the recovery of atrophic salivary glands, computed tomography (CT), and magnetic resonance imaging (MRI) of salivary glands will be conducted. The primary endpoint is the safety of the protocol. The secondary endpoints are the changes from baseline in whole saliva secretion and salivary gland atrophy. Discussion: This will be the first clinical study of regenerative therapy using E-MNCs for patients with severe radiation-induced xerostomia. The results of this study are expected to contribute to developing the low-invasive cell-based therapy for radiation-induced xerostomia.