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Melanocyte protein PMEL (gp100) peptide presented by HLA-A*02:01 (gp100/HLA-A*02:01)

Target
gp100/HLA-A*02:01
Molecular classification
Peptide-MHC complex, Tumor-associated antigen (TAA)
01

Overview

The gp100 antigen, also known as Melanocyte protein PMEL, is a lineage-specific protein involved in the biogenesis of melanosomes within melanocytes (UniProt P40967). In the context of immunotherapy, specific peptides derived from gp100 are presented on the cell surface by the Human Leukocyte Antigen (HLA) allele A*02:01, forming a peptide-MHC complex that can be recognized by T-cell receptors (TCRs) (PubMed: 35069587). This complex is highly expressed in both cutaneous and uveal melanoma, making it a significant therapeutic target (NCI Thesaurus). Drugs like tebentafusp utilize a bispecific TCR-anti-CD3 format to redirect T cells to kill gp100-expressing tumor cells (FDA Label: Kimmtrak). Because gp100 is also expressed in normal melanocytes, treatment can lead to on-target off-tumor effects such as vitiligo or ocular inflammation (PubMed: 22553346). Monitoring for HLA-A*02:01 status is essential for patient selection in these targeted therapies.

Other names
PMELPMEL17Silver locus protein homologMelanocyte lineage-specific antigen gp100ME20-MME20-Sgp100 antigen presented by HLA-A*0201
02

Mechanism of action

T-cell redirection via bispecific T-cell receptor (TCR)-anti-CD3 fusion proteins and T-cell activation via peptide vaccination (FDA Label: Kimmtrak; PubMed: 21632993).

03

Biological functions

Melanosome biogenesis (UniProt P40967)PigmentationImmune recognition
04

Disease associations

MelanomaUveal melanoma (PubMed: 35069587)
05

Safety considerations

Cytokine release syndrome (CRS) (FDA Label: Kimmtrak)On-target off-tumor skin toxicity (vitiligo, rash) (PubMed: 22553346)On-target off-tumor ocular toxicity (uveitis)Pyrexia
06

Interacting drugs

Tebentafusp

1 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotype (PubMed: 35069587)gp100 expression (NCI Thesaurus)

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