Immune Cell Therapy in IBD

Abstract

The therapeutic landscape of IBD has undergone a dramatic transformation since the advent of biologic therapies, especially TNF inhibitors. However, 30% of patients are primary nonresponders to biologic therapy and secondary failures are frequent. Due to substantial progress in our understanding of the biology of regulatory T cells (Tregs) and in the pathways of homing to the gastrointestinal tract, novel cell-based therapies for IBD have become possible. For example, although a reductionist view, one could envisage IBD as an imbalance between the proinflammatory effectors (such as Th17 cells) and the anti-inflammatory regulators (like Tregs). Here we focus on the development of ex vivo and in vivo approaches to enhance Tregs in the gastrointestinal tract. Specifically, herein we highlight a recently concluded phase 1/2a clinical trial that investigated the safety and efficacy of a single injection of escalating doses of autologous ovalbumin-specific Tregs in patients with active Crohn's disease refractory to conventional therapy. This therapy was well tolerated and demonstrated dose-related efficacy. We also discuss the potential of directing Tregs derived through intranasal as well as epicutaneous immunization to the gastrointestinal tract by enhancing their gut homing signature and their potential to decrease gastrointestinal inflammation. Finally, the strengths and pitfalls of these new therapeutic approaches are discussed as we move forward in this largely uncharted territory.

Expression of decorin in intestinal tissues of mice with inflammatory bowel disease and its correlation with autophagy

“…Inflammatory bowel disease (IBD) is a group of common chronic inflammatory gastrointestinal disorders, including Crohn's disease and ulcerative colitis (1,2). IBD usually occurs in young adults and is closely associated with inheritance, infection and immune function (3).…”

Identification of Candidate Genes Related to Inflammatory Bowel Disease Using Minimum Redundancy Maximum Relevance, Incremental Feature Selection, and the Shortest-Path Approach

“…Inflammation is a basic pathological process regulated by the immune system [ 99 ]. Therefore, the immune system plays an irreplaceable role in IBD [ 100 ]. Several predicted genes have been confirmed to be associated with the immune system and participate in the immune reaction.…”

“…As a receptor of significant biological signals, LEPROT (rank 10 in the mRMR feature list) encodes a crucial receptor of GH and has been reported to be associated with the initiation of inflammation in the intestine in mice [ 113 ]. IBD has been regarded to be the result of immune systematic disorders and autoimmune reactions [ 1 , 100 ]. Another gene, CLEC1B (rank 16 in the mRMR feature list), also participates in the development of IBD via the regulation of the intestinal immune system, especially the proliferation of NK cells and the formation of lymph nodes [ 114 ].…”

“…IBD is a common disease involving the digestive system, especially the intestinal tissue [ 1 ]. However, IBD has also been shown to be associated with carcinoma in the digestive system, especially colorectal cancer [ 100 ]. Several of our predicted genes are also involved in tumor initiation, where cells may have mutated in precancerous lesions, including severe IBD.…”

IL-10 downregulates CXCR3 expression on Th1 cells and interferes with their migration to intestinal inflammatory sites

“…Additionally, 30% of patients are primary non-responders to biological therapy and secondary failures are frequent. 4 Thus, there is an urgent need to develop new, more specific therapies for IBD that aim for the re-establishment of gut homeostasis by immunoregulatory rather than immunosuppressive mechanisms.…”