Indoleamine 2,3-dioxygenase 1-derived HLA-A2 peptide epitope (IDO1-HLA-A2 peptide)

The Indoleamine 2,3-dioxygenase 1 (IDO1)-derived HLA-A2 peptide epitope is a specific antigenic fragment of the IDO1 enzyme presented by the Human Leukocyte Antigen A2 (HLA-A2) complex on the cell surface (Sørensen et al., 2009). IDO1 is an intracellular enzyme that suppresses immune activity by degrading tryptophan into kynurenine, which inhibits T-cell proliferation and promotes the development of regulatory T cells (Munir et al., 2012). This epitope, particularly the sequence known as IDO5 (ALLEIASCL), is frequently overexpressed in the tumor microenvironment by both malignant cells and immunosuppressive myeloid cells (Kjeldsen et al., 2018). As a therapeutic target, this peptide is used in cancer vaccines to stimulate the expansion of endogenous IDO1-specific cytotoxic T lymphocytes (CTLs). These CTLs are capable of recognizing and lysing IDO1-expressing cells, thereby neutralizing a key mechanism of tumor-mediated immunosuppression (IO Biotech, 2023). Clinical development of drugs like IO102 focuses on using this epitope to enhance the efficacy of other immunotherapies, such as PD-1/PD-L1 inhibitors, in patients with advanced solid tumors (Kjeldsen et al., 2018).

Other names

IDO1 peptideIDO5 peptideIDO1-derived epitopeALLEIASCL peptideIDO1-A2 epitope

The target acts as an antigen that, when administered as a vaccine (e.g., IO102), stimulates the expansion of endogenous IDO1-specific CD8+ T cells. These T cells recognize the IDO1-derived peptide presented by HLA-A2 on the surface of tumor cells and immunosuppressive immune cells, leading to their targeted destruction and the reversal of tumor-induced immune suppression (Sørensen et al., 2009; Kjeldsen et al., 2018).