Preferentially expressed antigen in melanoma (PRAME) peptide-HLA complex (PRAME-HLA)

Preferentially expressed antigen in melanoma (PRAME) is a cancer-testis antigen (CTA) that functions as a ligand-dependent co-repressor of the retinoic acid receptor (RAR), thereby inhibiting differentiation and promoting tumor cell survival [1]. While its expression is restricted to the testis and a few other immune-privileged sites in healthy adults, it is highly overexpressed in a wide range of hematological and solid malignancies [2]. The therapeutic target specifically consists of PRAME-derived peptides (such as the VLDGLDVLL decamer) presented on the cell surface by Major Histocompatibility Complex (MHC) Class I molecules, most commonly HLA-A*02:01 [3]. This peptide-MHC complex is recognized by high-affinity T-cell receptors (TCRs), allowing the immune system to target the intracellular PRAME protein which is otherwise inaccessible to standard antibody therapies [4]. Current drug development focuses on TCR-engineered T-cell therapies (TCR-T) and bispecific TCR-based T-cell engagers (ImmTACs) that redirect cytotoxic T lymphocytes to kill PRAME-positive cancer cells [5]. Clinical trials for agents like IMA203 and IMC-F106C have demonstrated promising efficacy in patients with advanced solid tumors, highlighting the target's potential for precision immunotherapy [6]. Citations: [1] UniProt P78395; [2] PubMed 10748128; [3] PubMed 28972014; [4] Immatics (IMA203); [5] Immunocore (IMC-F106C); [6] ClinicalTrials.gov NCT03686124.

Other names

PRAMEMelanoma antigen preferentially expressedMAPEOIP4OPA-interacting protein 4PRAME-derived peptide-MHC class I complex

T-cell receptor (TCR) mediated recognition of specific PRAME peptides presented on MHC Class I molecules, leading to T-cell activation, cytokine release, and targeted lysis of tumor cells.