Insulin receptor substrate 2 (IRS2) phosphopeptide epitope (IRS2 phosphopeptide)

The Insulin receptor substrate 2 (IRS2) phosphopeptide epitope is a post-translationally modified tumor-associated antigen (TAA) presented by MHC Class I molecules, most notably HLA-A*02:01 (Zarling et al., 2000, Journal of Experimental Medicine). IRS2 itself is a critical cytoplasmic signaling adapter that mediates the intracellular effects of insulin and insulin-like growth factor 1 (IGF-1) receptors, influencing cellular growth, survival, and metabolism (UniProt P81274). In various malignancies such as melanoma and ovarian cancer, dysregulated kinase activity leads to the aberrant phosphorylation and subsequent presentation of specific IRS2 peptide fragments, such as the RVApSPTSGV sequence, which are recognized by the immune system as 'altered self' (Engelhard et al., 2006, Current Opinion in Immunology). These phosphopeptides are highly attractive targets for immunotherapy because they are often tumor-specific or significantly enriched in cancer cells compared to normal tissues. Current therapeutic strategies under investigation include synthetic phosphopeptide-based vaccines and T-cell receptor (TCR) engineered T-cell therapies designed to selectively eliminate cells displaying these markers. However, the clinical application of these targets must address challenges such as the stability of the phosphorylation modification and the potential for tumor escape through the loss of MHC expression.

Other names

pIRS2 epitopePhosphorylated insulin receptor substrate 2 antigenIRS2 phospho-antigenIRS2(pS1100) epitopeRVApSPTSGV

Induction of antigen-specific cytotoxic T-lymphocyte (CTL) responses against tumor cells presenting the phosphorylated IRS2 peptide on MHC Class I molecules.