Tryptophan-2,3-dioxygenase (TDO) is an enzyme catalyzing the initial step in the kynurenine pathway, catalyzing L-tryptophan into kynurenine. Like IDO, TDO, by deprivation of tryptophan and by generation of kynurenine, contributes to immune suppression by inhibiting the proliferation of immune cells. However, unlike IDO, TDO specifically catabolizes L-tryptophan (whilst IDO breaks down both D- and L-tryptophan) and is expressed constitutively in the liver and the brain.
TDO is expressed in many tumors, including glioma, breast cancer, lung cancer and colorectal cancer, and the expression is distinct from IDO. Further, in tumors where both TDO and IDO are expressed, TDO and IDO are expressed in different regions of the same tumor, implying that IDO and TDO are not redundant and play different roles in tumors and immune evasion.
IO Biotech's lead anti-cancer therapy targeting TDO is IO130.