Immunological influence of serum-free manufactured umbilical cord-derived mesenchymal stromal cells for steroid-resistant acute graft-versus-host disease.
Immunological influence of serum-free manufactured umbilical cord-derived mesenchymal stromal cells for steroid-resistant acute graft-versus-host disease.
复制标题
无血清制造的脐带源间充质基质细胞对类固醇耐药的急性移植物抗宿主病的免疫学影响。
DOI：
10.1007/s12185-022-03408-7
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发表时间：
2022
期刊：
影响因子：
2.1
通讯作者：
Arinobu Tojo.
中科院分区：
文献类型：
--
作者：
Tokiko Nagamura-Inoue;Seiko Kato;Yuho Najima;Masamichi Isobe;Noriko Doki;Hisashi Yamamoto;Naoyuki Uchida;Atsuko Takahashi;Akiko Hori;Masanori Nojima;Kazuteru Ohashi;Fumitaka Nagamura;Arinobu Tojo.
本研究探讨了在无血清培养基和冷冻保护剂中处理的同种异体脐带间充质基质细胞（IMSUT-CORD）治疗类固醇耐药急性移植物抗宿主病（aGVHD）的安全性、有效性和免疫学影响。在一项I期剂量递增试验中，IMSUT-CORD每周两次静脉输注，持续两个周期，最多额外两个周期。4例患者接受了1 × 106个细胞/kg的剂量，3例接受了2 × 106个细胞/kg的剂量。在总共76起不良事件中，14起相关或可能相关不良事件包括2例潮热、头痛和周围神经病变，上腹痛、缺氧、γ-GTP升高、嗜睡、注射部位外周血管疼痛、血小板减少症、高血压和纤维蛋白原降低各1例。在初始IMSUT-CORD输注后16周，3例患者显示完全缓解（CR），2例部分缓解（PR），1例混合缓解，1例无缓解。总有效率为71.4%，CR/PR后28天以上的持续CR/PR率为100%。NK细胞计数显著增加，与治疗反应相关，而IL-12、IL-17和IL-33水平降低，但与治疗反应无关。IMSUT-CORD治疗期间CCL 2和CCL 11水平升高。IMSUT-CORD可用于类固醇耐药aGVHD患者（UMIN 000032819：https：//www.umin.ac.jp/ctr）。
This study investigated the safety, efficacy, and immunological influence of allogeneic umbilical cord-derived mesenchymal stromal cells (IMSUT-CORD) processed in serum-free medium and cryoprotectant, for treating steroid-resistant acute graft-versus-host disease (aGVHD). In a phase I dose-escalation trial, IMSUT-CORD were infused intravenously twice weekly over two cycles with up to two additional cycles. Four patients received a dose of 1 × 106cells/kg, while three received 2 × 106/kg. Of 76 total adverse events, fourteen associated or possibly associated adverse events included 2 cases of a hot flash, headache, and peripheral neuropathy, 1 each of upper abdominal pain, hypoxia, increased γ-GTP, somnolence, peripheral vascular pain at the injection site, thrombocytopenia, hypertension, and decreased fibrinogen. At 16 weeks after the initial IMSUT-CORD infusion, three patients showed complete response (CR), two partial response (PR), one mixed response, and one no response. The overall response rate was 71.4%, and the continuous CR/PR rate was 100% for over 28 days after CR/PR. NK cell count significantly increased and correlated with treatment response, whereas IL-12, IL-17, and IL-33 levels decreased, but did not correlate with treatment response. CCL2 and CCL11 levels increased during IMSUT-CORD therapy. IMSUT-CORD are usable in patients with steroid-resistant aGVHD (UMIN000032819: https://www.umin.ac.jp/ctr).