如今，结肠炎（肠道炎症）的治疗依赖于诱导与系统性不良事件（包括反复感染）相关的免疫抑制。这种治疗策略对于越来越多患有免疫检查点抑制剂 (ICI) 诱导的结肠炎的癌症患者来说尤其存在问题，因为免疫抑制也会干扰 ICI 治疗反应。因此，需要减少炎症并增强肠道愈合的局部作用治疗。在这里，我们研究了细菌将短寿命免疫调节趋化因子传递到结肠炎小鼠发炎肠道的效果和安全性。单独使用 DSS 或与 ICI（抗 PD1、抗 CTLA-4）联合诱导结肠炎，并口服经基因修饰表达趋化因子 CXCL12-1α（R2LC_CXCL12、emimogene sigulactibac）的罗伊氏乳杆菌 R2LC。此外，还在兔子身上评估了配制的候选药物 ILP100-Oral 的药理学和安全性。口服产生 CXCL12 的罗伊氏乳杆菌 R2LC 在患有明显 DSS 和 ICI 诱导结肠炎的小鼠中，两天后就显着改善了结肠炎症状，在基准实验中证明其优于抗 TNF-α、抗 α4ꞵ7 和皮质类固醇的治疗。作用机制涉及趋化因子递送至派尔氏淋巴结 (PP)（通过局部 CXCR4 信号转导证实）以及表达 IL-10 和 TGF-β1 的结肠调节性免疫细胞数量增加。在小鼠中未检测到全身暴露或植入，并且在兔子中证实了产品的可行性、药理学和安全性。总之，口服产生CXCL12的罗伊氏乳杆菌R2LC可有效改善结肠炎并增强粘膜愈合，并且具有良好的安全性。

Treatments of colitis, inflammation of the intestine, is today relying on induction of immune suppression associated with systemic adverse events including recurrent infections. This treatment strategy is specifically problematic in the increasing population of cancer patients with immune checkpoint inhibitor (ICI)-induced colitis, as immune suppression also interferes with the ICI-treatment response. Thus, there is a need for local-acting treatments which reduce inflammation and enhance intestinal healing. Here, we investigated the effect and safety of bacterial delivery of short-lived immunomodulating chemokines to the inflamed intestine in mice with colitis. Colitis was induced by DSS alone or in combination with ICI (anti-PD1, anti-CTLA-4) and L. reuteri R2LC genetically modified to express the chemokine CXCL12-1α (R2LC_CXCL12, emilimogene sigulactibac) was given perorally. In addition, pharmacology and safety of the formulated drug candidate, ILP100-Oral, was evaluated in rabbits. Peroral CXCL12-producing L. reuteri R2LC significantly improved colitis symptoms already after 2 days in mice with overt DSS and ICI-induced colitis, which in benchmarking experiments was demonstrated to be superior to treatments with anti-TNF-α, anti-α4ꞵ7 and corticosteroids. The mechanism of action involved chemokine delivery to Peyer´s Patches (PPs), confirmed by local CXCR4 signaling, and increased numbers of colonic, regulatory immune cells expressing IL-10 and TGF-β1. No systemic exposure or engraftment could be detected in mice, and product feasibility, pharmacology and safety were confirmed in rabbits. In conclusion, peroral CXCL12-producing L. reuteri R2LC efficiently ameliorates colitis and enhances mucosal healing, and has a favorable safety profile.