Target intelligence / Profile preview

Melanoma-associated antigen peptide-HLA-A*0201 complex (MAA-HLA-A*0201)

Target
MAA-HLA-A*0201
Molecular classification
Peptide-MHC complex, Antigen, MHC Class I
01

Overview

Melanoma-associated antigen (MAA) peptides presented by the Human Leukocyte Antigen (HLA)-A*0201 allele represent a specialized class of immunotherapy targets consisting of intracellular protein fragments displayed on the cell surface. These targets, such as peptides derived from MAGE-A4, gp100, and NY-ESO-1, are processed by the cellular machinery and presented by the MHC Class I molecule HLA-A*0201 (Source: Nature Reviews Drug Discovery, 2021). Because these antigens are frequently overexpressed in melanoma and other malignancies but have limited expression in normal tissues, they provide a window for selective tumor targeting (Source: Journal for ImmunoTherapy of Cancer, 2020). Therapeutic interventions targeting these complexes include T-cell receptor (TCR) engineered T-cells and bispecific TCR-based engagers, which allow the immune system to recognize and eliminate cells based on their internal proteome (Source: NEJM, 2021). Notable examples include Tebentafusp, which targets the gp100 peptide-HLA complex, and Afamitresgene autoleucel, which targets MAGE-A4 (Source: Nature Medicine, 2024). The clinical success of these therapies depends heavily on the precise matching of the patient's HLA type and the tumor's antigen expression profile (Source: Lancet Oncology, 2023).

Other names
MAGE-A4/HLA-A*02:01gp100/HLA-A*02:01MART-1/HLA-A*02:01NY-ESO-1/HLA-A*02:01Melanoma antigen-MHC complexpMHC complexMelanoma-associated antigen peptides presented by HLA-A2
02

Mechanism of action

T-cell receptor (TCR) mediated recognition of specific intracellular-derived peptides presented on the cell surface by HLA-A*0201, leading to the recruitment and activation of cytotoxic T-cells against tumor cells.

03

Biological functions

Antigen presentationImmune responseT-cell activationCD8+ T-cell recognition
04

Disease associations

MelanomaCancerSolid tumorsSynovial sarcoma
05

Safety considerations

Off-target toxicity due to cross-reactivity with similar peptides in healthy tissuesCytokine release syndrome (CRS)Immune effector cell-associated neurotoxicity syndrome (ICANS)On-target off-tumor toxicity
06

Interacting drugs

Tebentafusp

3 more in the full profile.

07

Biomarkers

HLA-A*02:01 genotypeMAGE-A4 expressiongp100 expressionNY-ESO-1 expressionMART-1 expression

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