T-cell receptors recognizing IDO1 peptide–HLA complexes (IDO1-TCR)

T-cell receptors (TCRs) recognizing IDO1 peptide–HLA complexes are specialized immune receptors that target cells expressing Indoleamine 2,3-dioxygenase 1 (IDO1), a critical enzyme involved in tumor-mediated immunosuppression (Andersen et al., 2020; iobiotech.com). IDO1 is frequently upregulated in the tumor microenvironment (TME) by both malignant cells and regulatory immune cells, where it catalyzes the degradation of tryptophan into kynurenine, leading to T-cell anergy and the recruitment of regulatory T cells (nih.gov; frontiersin.org). TCRs specific for IDO1-derived peptides, such as the HLA-A2-restricted IDO1-5 (ALLEIASCL) or IDO1-199 (LAVPELSAL) sequences, allow cytotoxic T lymphocytes to identify and kill these immunosuppressive cells (nih.gov; researchgate.net). This targeting strategy aims to modulate the TME from a suppressive state to an inflamed, immune-active state, thereby enhancing the efficacy of other immunotherapies (iobiotech.com; asco.org). Clinical applications include the development of peptide vaccines like IO102, which induce these specific TCR-bearing T cells in vivo, and experimental TCR-T cell therapies designed for adoptive transfer (cancer.gov; esmo.org). These therapies are often evaluated in combination with PD-1/PD-L1 checkpoint inhibitors to overcome resistance mechanisms in solid tumors like melanoma and non-small cell lung cancer (iobiotech.com; nih.gov).

Other names

IDO1-specific T-cell receptorsIDO-specific TCRsIDO1-HLA-A2 specific TCRsIDO1-peptide-MHC specific TCRsIndoleamine 2,3-dioxygenase 1-specific T-cell receptors

The mechanism involves the activation and expansion of T cells carrying TCRs that specifically recognize IDO1-derived peptides presented by HLA molecules on the surface of tumor cells and immunosuppressive cells. Upon recognition, these T cells exert direct cytotoxic effects, lysing the target cells and reducing the metabolic immunosuppression caused by IDO1 activity, thereby promoting a more robust anti-tumor immune response (iobiotech.com; nih.gov).