Indoleamine 2,3-dioxygenase 1-derived peptide–HLA-A*02:01 complex (IDO-peptide/HLA-A2 complex)

The Indoleamine 2,3-dioxygenase 1 (IDO1)-derived peptide–HLA-A*02:01 complex is a therapeutic target used to stimulate the immune system against immunosuppressive environments in cancer. IDO1 is an enzyme that degrades tryptophan into kynurenine, a process that inhibits T-cell function and promotes immune evasion (Munn & Mellor, 2013, Science). Specific peptides derived from IDO1, such as the IDO5 epitope (ALLEIASCL), are presented on the cell surface by HLA-A*02:01 molecules (Andersen, 2012, Cancer Immunology, Immunotherapy). These complexes are recognized by naturally occurring IDO-specific cytotoxic T cells (CTLs). Therapeutic vaccines like IO102 are designed to expand these CTL populations, which then selectively target and kill IDO-expressing cells, including both tumor cells and regulatory immune cells like myeloid-derived suppressor cells (Sørensen et al., 2011, PLoS ONE). This dual action helps to directly reduce tumor mass and simultaneously alleviate the metabolic suppression of the tumor microenvironment. Clinical development of this target has shown promise in combination with PD-1 inhibitors for treating advanced melanoma and other solid tumors (IO Biotech, 2023).

Other names

IDO1 peptide-MHC complexIDO-derived epitopeIDO5 peptide-HLA-A2 complexIDO-specific T-cell targetIndoleamine 2,3-dioxygenase 1-derived peptide presented by HLA-A2

Vaccination with IDO-derived peptides induces the expansion of IDO-specific cytotoxic T lymphocytes (CTLs) that recognize and lyse IDO-expressing cells, such as tumor cells and immunosuppressive immune cells (e.g., regulatory T cells and myeloid-derived suppressor cells), thereby reversing tumor-induced immune suppression.