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PRAME peptide 100–108–HLA-A*02:01 peptide–major histocompatibility complex class I complex (PRAME_100–108/HLA-A*02:01 pMHC)

Target
PRAME_100–108/HLA-A*02:01 pMHC
Molecular classification
Major histocompatibility complex class I ligand (peptide–MHC complex), Antigen complex
01

Overview

The PRAME_100–108/HLA-A*02:01 peptide–MHC complex is a molecular structure formed when a specific peptide fragment derived from the PRAME (Preferentially Expressed Antigen in Melanoma) protein—residues 100 to 108—is presented on the surface of cells by the major histocompatibility complex class I molecule HLA-A*02:01. This complex is recognized by cytotoxic T lymphocytes and is being pursued as a therapeutic target in cancer immunotherapy, particularly in malignancies where PRAME is overexpressed, such as acute myeloid leukemia and certain solid tumors. Drugs targeting the complex aim to direct T cells or T cell receptor-mimic antibodies to kill cancer cells in an HLA-restricted, antigen-specific manner.

Other names
PRAME_100–108/HLA-A2 complexPRAME/HLA-A*02:01 pMHCPRAME epitope-HLA-A2 complex
02

Mechanism of action

T cell receptor mimicry: drugs or antibodies recognize the peptide–MHC complex and trigger T-cell mediated cytotoxicity Adoptive T cell therapy: T cells engineered to express TCRs specific for PRAME_100–108/HLA-A*02:01 recognize and kill tumor cells

03

Biological functions

Immune response (target for cytotoxic T lymphocyte recognition)Antigen presentation
04

Disease associations

Cancer (notably in acute myeloid leukemia and solid tumors)Other (potential roles in monitoring immune therapies)
05

Safety considerations

On-target, off-tumor toxicity (if PRAME or HLA-A*02:01–PRAME complexes are present in healthy tissues)Cytokine release syndrome (with T cell engaging therapies)Potential development of resistance via antigen or HLA loss
06

Interacting drugs

Tebentafusp (a TCR–CD3 bispecific fusion, primarily for NY-ESO-1 and gp100 pMHC, but development of similar drugs for PRAME is ongoing)

1 more in the full profile.

07

Biomarkers

Expression of PRAME mRNA/protein in tumor cells (selection for therapy)HLA-A*02:01 positivity in patients (patient selection for therapy)

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