Arginase 1 antigenic peptides presented on MHC (ARG1-pMHC)

Arginase 1 (ARG1) is a metabolic enzyme that plays a dual role as a urea cycle component in the liver and a potent immunosuppressor in the tumor microenvironment [9, 14]. In many cancers, ARG1 is highly expressed by myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), where it depletes L-arginine, an essential amino acid for T-cell function [8, 10]. The target "Arginase 1 antigenic peptides presented on MHC" consists of specific ARG1-derived peptide sequences displayed on the surface of these cells by MHC Class I and II molecules [1, 2]. Therapeutic interventions, such as the peptide vaccine IO112, are designed to stimulate the immune system to produce ARG1-specific CD4+ and CD8+ T cells [2, 11]. These activated T cells recognize the ARG1-pMHC complexes and exert anti-tumor effects by directly lysing immunosuppressive cells or by secreting pro-inflammatory cytokines like IFN-gamma [3, 4, 6]. This process effectively "reprograms" the tumor microenvironment from an anti-inflammatory to a pro-inflammatory state, restoring L-arginine levels and enhancing the efficacy of other immunotherapies [10, 12]. Clinical trials have demonstrated that targeting these peptides is safe and can induce robust immune responses in patients with various solid tumors [2, 8]. By removing the metabolic block of arginine depletion, this target enhances the overall anti-tumor immune response [10]. Overall, this target represents a novel approach to metabolic-immune checkpoint modulation in oncology [1, 13].

Other names

Arginase-1 MHC-peptide complexARG1-derived epitopesArginase-1 T-cell epitopesARG1-pMHC

Induction of ARG1-specific T-cell responses to target and eliminate or reprogram ARG1-expressing immunosuppressive cells in the tumor microenvironment [3, 8].