Autologous regulatory T-cell transfer in refractory ulcerative colitis with concomitant primary sclerosing cholangitis

Abstract

ObjectiveUlcerative colitis (UC) is a chronic, debilitating immune-mediated disease driven by disturbed mucosal homeostasis, with an excess of intestinal effector T cells and an insufficient expansion of mucosal regulatory T cells (Tregs). We here report on the successful adoptive transfer of autologous, ex vivo expanded Tregs in a patient with refractory UC and associated primary sclerosing cholangitis (PSC), for which effective therapy is currently not available.DesignThe patient received a single infusion of 1×106 autologous, ex vivo expanded, polyclonal Tregs per kilogram of body weight, and the clinical, biochemical, endoscopic and histological responses were assessed 4 and 12 weeks after adoptive Treg transfer.ResultsThe patient showed clinical, biochemical, endoscopic and histological signs of response until week 12 after adoptive Treg transfer, which was associated with an enrichment of intestinal CD3+/FoxP3+ and CD3+/IL-10+ T cells and increased mucosal transforming growth factor beta and amphiregulin levels. Moreover, there was marked improvement of PSC with reduction of liver enzymes. This pronounced effect lasted for 4 weeks before values started to increase again.ConclusionThese findings suggest that adoptive Treg therapy might be effective in refractory UC and might open new avenues for clinical trials in PSC.Trial registration numberNCT04691232.

Bifidobacterium breve Protects the Intestinal Epithelium and Mitigates Inflammation in Colitis via Regulating the Gut Microbiota–Cholic Acid Pathway

“…IBD is a chronic and nonspecific inflammatory condition characterized by ulceration and damage to the colonic mucosa. 20 Bifidobacterium strains are essential for infants as they promote intestinal homeostasis and immune system development. Bifidobacterium strains, which are simultaneously most abundant in the infant's gut, can be vertically transmitted through breast milk, resulting in a higher presence of Bifidobacterium in breastfed infants compared to nonbreastfed counterparts.…”

Current and Emerging Targeted Therapies for Ulcerative Colitis

“…Newly developed therapies, like IL-23 inhibitors, TLR-9 agonists, sIL-6R Therapies in Ulcerative Colitis inhibitors, and upregulators of micro-RNA, not only offer novel treatment approaches but also enable us to gather more insights into disease pathogenesis. Currently conducted cell-based therapy trials that investigate effectiveness of regulatory T-cell transfer might further expand our treatment approaches for the benefit of patients [43]. Combination or sequential use of advanced therapies warrants further investigation, as they might offer heightened efficacy, but long-term safety needs to be studied in these endeavors.…”

Targeting regulatory T cell metabolism in disease: Novel therapeutic opportunities

“…Preclinical and clinical research has demonstrated strong potential for Treg-based immunotherapies in the prevention or treatment of graft-versus-host disease, organ transplant rejection, and a variety of autoimmune diseases, such as type 1 diabetes, multiple sclerosis (MS), celiac disease, and inflammatory bowel disease [6][7][8][9][10][11]. In these therapies, Tregs-either polyclonal or genetically engineered to express antigen-specific T-cell receptors (TCR-Tregs) or chimeric antigen receptors (CARs-Tregs)-are expanded ex vivo prior to reinfusion as an adoptive cell therapy (ACT) [7,9,11].…”