B2*
Desaminotyrosine (DAT) as a GvHD Preventive/Therapeutic Adjuvant and Immunotherapy Outcome Predictor
Dr Erik Thiele Orberg, Universitätsklinikum Regensburg; Prof. Hendrik Poeck, Universitätsklinikum Regensburg; Sascha Göttert, Universitätsklinikum Regensburg
Bayerische Patentallianz GmbH
Challenge
Immunotherapies have become very important in the prevention and treatment of cancers. However, the efficiency of immunotherapies is still limited. For example, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for many otherwise incurable hematological cancers, yet, its success is limited by the severe morbidity and mortality associated with graft-versus-host disease (GvHD), characterized by an allogeneic immune reaction of donor T cells directed against the recipient’s organs, especially the skin, intestine, and liver. Additionally, prediction of survival and relapse after allo-HSCT remains challenging.
Technology
The invention describes a way to improve outcomes of allo-HSCT by leveraging the microbiome and its metabolites to modulate graft-versus-host disease (GvHD) while preserving graft-versus-leukemia (GvL) effects. Integrated analyses of bacterial components in allo-HSCT patients carried out by the inventors revealed a microbiome signature that correlated with immuno-modulatory metabolites (IMMs) and improved survival, highlighted by the established Immuno-modulatory Metabolite Risk Index (IMM-RI). Preclinical work further describes DAT, a microbial metabolite, as promoting intestinal regeneration and balancing GvL and GvHD through mTORC1- and STING–dependent pathways—thereby providing implications for precision microbiome-based therapies. Desaminotyrosine (DAT) is a microbial metabolite produced during bacterial flavonoid metabolism and has been shown to protect intestinal barrier integrity and promote regeneration of intestinal stem cells during allogeneic hematopoietic stem cell transplantation (allo-HSCT). DAT activates key cellular pathways to reduce graft-versus-host disease (GvHD) while enhancing graft-versus-leukemia (GvL) responses, offering a novel microbiome-based approach to improve transplant outcomes and minimize complications through specific metabolite formulations as adjunct therapies in allo-HSCT. Together, these findings support a strategy to deploy metabolite-producing microbial consortia and metabolite formulations to personalize therapy, protect the intestinal barrier, and optimize both survival and disease control after allo-HSCT.
Commercial Opportunity
There is growing interest in microbiome-derived metabolites in immunotherapy and tissue regeneration. The global market for microbiome therapeutics was estimated in 2022 at 94.86 million USD and is projected to grow to 2030 at a CAGR of 35.32%. The present invention: • Enables prediction of patient outcomes post-allo-HSCT • Supports development of precision microbiome therapies including synthetic consortia and metabolite supplementation • Offers pathways to mitigate GvHD severity and reduce relapse rates via microbiome modulation • Provides a foundation to improve other T cell-mediated therapies influenced by gut microbiota such as CAR-T and immune checkpoint inhibitors • Facilitates future clinical assays for rapid metabolite and biomarker measurement enabling personalized treatment strategies
Development Status
The inventors have investigated the efficacy of DAT in in vitro and in vivo data as well as in human samples from healthy subjects and patients. Further in vivo data are generated at the moment.
Patent Situation
Filed in EP
Further Reading
doi:10.1038/s43018-023-00669-x
doi:10.1038/s41467-025-65180-6
