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EcN-IAA is a preclinical-stage engineered live biotherapeutic product (LBP) built on the probiotic *Escherichia coli* Nissle 1917 (EcN) chassis. The strain is genetically modified to carry a heterologous biosynthetic pathway that enables the secretion of indole-3-acetic acid (IAA), a microbial metabolite and agonist of the aryl hydrocarbon receptor (AhR). To optimize IAA production and prevent the generation of native indole, the endogenous tryptophanase gene (*tnaA*) is knocked out. EcN-IAA is being investigated for its immunomodulatory and therapeutic potential in oncology and autoimmune disorders. In preclinical models of colorectal cancer, intratumoral administration of EcN-IAA alters the tumor microenvironment by increasing CXCL9 and IFN-γ levels, enhancing the infiltration and activation of CD4+ and CD8+ T cells, and suppressing tumor growth. In models of multiple sclerosis (experimental autoimmune encephalomyelitis), oral administration of EcN-IAA activates AHR-KLF4-FADS3 signaling in intestinal dendritic cells, boosting docosahexaenoic acid (DHA) production and suppressing encephalitogenic T cells.
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