Major histocompatibility complex-arginase 1 peptide complex (MHC-ARG1) (MHC-ARG1)

The Major Histocompatibility Complex (MHC)-arginase 1 peptide complex is a therapeutic target consisting of peptides derived from the Arginase-1 (ARG1) enzyme presented on the surface of cells by MHC molecules (Martinenaite et al., 2018, Communications Biology). Arginase-1 is a manganese-containing enzyme that catalyzes the conversion of L-arginine to L-ornithine and urea, playing a critical role in the urea cycle (UniProt P05089). In the context of oncology, ARG1 is frequently overexpressed by myeloid-derived suppressor cells (MDSCs) and certain tumor cells, leading to the depletion of L-arginine in the tumor microenvironment (Steggerda et al., 2017, JITC). This depletion profoundly inhibits T-cell proliferation and activation, facilitating immune evasion by the tumor. By targeting the MHC-ARG1 peptide complex, immunotherapies such as the peptide vaccine IO101 aim to stimulate the host's immune system to generate ARG1-specific T cells (IO Biotech, 2024). These T cells can then selectively identify and eliminate the immunosuppressive cells within the tumor microenvironment, thereby restoring anti-tumor immunity. This approach is particularly novel as it targets the metabolic defense mechanisms of the tumor rather than the tumor cells themselves, potentially providing a synergistic effect when combined with other checkpoint inhibitors.

Other names

HLA-arginase 1 complexARG1 peptide-MHC complexArginase-1-derived peptide-MHC complexMHC-presented ARG1 peptides

Vaccine-mediated induction of ARG1-specific cytotoxic T lymphocytes that recognize and eliminate cells presenting Arginase-1 peptides on MHC molecules, thereby reducing immunosuppression in the tumor microenvironment (Martinenaite et al., 2018).