Qu Biologics Inc., Vancouver, BC, Canada.
Division of Gastroenterology, Department of Pediatrics, BC Children's Hospital Research Institute (BCCHRI), University of British Columbia, Vancouver, BC, Canada.
Front Immunol. 2018 Sep 27;9:2211. doi: 10.3389/fimmu.2018.02211. eCollection 2018.
Current ulcerative colitis (UC) treatments are focused on symptom management primarily via immune suppression. Despite the current arsenal of immunosuppressant treatments, the majority of patients with UC still experience disease progression. Importantly, aggressive long-term inhibition of immune function comes with consequent risk, such as serious infections and malignancy. There is thus a recognized need for new, safe and effective treatment strategies for people living with UC that work upstream of managing the symptoms of the disease. The objective of this study was to evaluate a microbial-based treatment, QBECO, that functions to productively activate rather than suppress mucosal immune function as a novel approach to treat UC. Two established models of experimental colitis, namely chemically-induced DSS colitis and the spontaneous colitis that develops in deficient mice, were used to assess whether QBECO treatment could ameliorate gastrointestinal disease. A small exploratory 16-week QBECO open-label trial was subsequently conducted to test the safety and tolerability of this approach and also to determine whether similar improvements in clinical disease and histopathology could be demonstrated in patients with moderate-to-severe UC. QBECO treatment successfully reduced inflammation and promoted mucosal and histological healing in both experimental models and in UC patients. The preclinical models of colitis showed that QBECO ameliorated mucosal pathology, in part by reducing inflammatory cell infiltration, primarily that induced by neutrophils and inflammatory T cells. The most rapid and noticeable change observed in QBECO treated UC patients was a marked reduction in rectal bleeding. Collectively, this work demonstrates for the first time that strategically activating immune function rather than suppressing it, not only does not worsen colitis induced-damage, but may lead to an objective reduction in UC disease pathology.
目前的溃疡性结肠炎 (UC) 治疗方法主要侧重于通过免疫抑制来控制症状。尽管目前有大量的免疫抑制治疗方法，但大多数 UC 患者仍会出现疾病进展。重要的是，长期积极抑制免疫功能会带来相应的风险，如严重感染和恶性肿瘤。因此，人们认识到需要为 UC 患者开发新的、安全有效的治疗策略，这些策略可以在上游管理疾病症状之前发挥作用。本研究的目的是评估一种基于微生物的治疗方法 QBECO，该方法通过生产性地激活而不是抑制黏膜免疫功能，作为治疗 UC 的一种新方法。本研究使用了两种已建立的实验性结肠炎模型，即化学诱导的 DSS 结肠炎和自发性结肠炎（在缺陷小鼠中发展），以评估 QBECO 治疗是否可以改善胃肠道疾病。随后进行了一项小规模的探索性 16 周 QBECO 开放性标签试验，以测试该方法的安全性和耐受性，并确定在中度至重度 UC 患者中是否可以证明类似的临床疾病和组织病理学改善。QBECO 治疗成功地减轻了两种实验模型和 UC 患者的炎症，并促进了黏膜和组织学愈合。结肠炎的临床前模型表明，QBECO 通过减少炎症细胞浸润，主要是中性粒细胞和炎症性 T 细胞的浸润，改善了黏膜病理学。在 QBECO 治疗的 UC 患者中观察到的最快速和最明显的变化是直肠出血明显减少。总之，这项工作首次证明，策略性地激活免疫功能而不是抑制它，不仅不会加重结肠炎引起的损伤，反而可能导致 UC 疾病病理学的客观减轻。
