Peptide-Major Histocompatibility Complex presenting Wilms tumor protein 1, Preferentially expressed antigen in melanoma, and Baculoviral IAP repeat-containing protein 5 epitopes (pMHC (WT1/PRAME/Survivin))

Peptide-Major Histocompatibility Complex (pMHC) complexes presenting epitopes from Wilms tumor protein 1 (WT1), Preferentially expressed antigen in melanoma (PRAME), and Baculoviral IAP repeat-containing protein 5 (Survivin) are critical targets for cancer immunotherapy. These complexes consist of short peptide fragments derived from intracellular proteins that are processed and presented on the cell surface by Major Histocompatibility Complex (MHC) Class I molecules, typically HLA-A*02:01 (PubMed: 31110039). WT1 is a transcription factor overexpressed in various hematological malignancies and solid tumors, where it plays a role in cell proliferation and survival (PubMed: 17464059). PRAME is a cancer-testis antigen that is frequently expressed in melanoma, non-small cell lung cancer, and leukemias, acting as a repressor of retinoic acid signaling (PubMed: 28630100). Survivin is an inhibitor of apoptosis protein (IAP) that is highly expressed in nearly all human cancers but absent in most normal adult tissues, making it a highly specific target for inducing tumor cell death (PubMed: 15150571). Therapeutic interventions targeting these pMHC complexes include T-cell receptor (TCR) engineered T-cells, TCR-like antibodies, and peptide-based vaccines, which aim to harness the specificity of the immune system to eliminate tumor cells while sparing healthy tissue (PubMed: 25608570). These therapies are particularly valuable for targeting intracellular oncogenic drivers that are otherwise inaccessible to conventional antibody-based drugs (PubMed: 30030295).

Other names

HLA-peptide complexesTumor-associated antigen epitopesMHC-restricted tumor antigenspMHC complexes

Recognition by T-cell receptors (TCRs) or TCR-like antibodies leading to MHC-restricted cytotoxic T-lymphocyte (CTL) activation and tumor cell lysis.