Target intelligence / Profile preview

Melanoma-associated antigen peptide-HLA-A*0201 complexes (pMHC complexes (MAGE-3/Melan-A/gp100/NA17))

Target
pMHC complexes (MAGE-3/Melan-A/gp100/NA17)
Molecular classification
Peptide-MHC Class I complex, Antigenic complex
01

Overview

The target consists of a specific set of melanoma-associated peptides—MAGE-3, Melan-A (MART-1), gp100, and NA17—presented by the Human Leukocyte Antigen (HLA)-A*0201 molecule on the surface of autologous peripheral blood mononuclear cells (PBMCs) (Banchereau et al., 2001). These peptide-MHC (pMHC) complexes serve as the primary recognition units for the cellular immune system, specifically for CD8+ cytotoxic T lymphocytes (CTLs) (Godelaine et al., 2003). In a therapeutic context, these complexes are typically generated by pulsing a patient's own immune cells, such as dendritic cells derived from PBMCs, with synthetic peptides to create a personalized cancer vaccine (Guilloux et al., 1996). The goal is to prime and expand T-cell populations that can specifically identify and destroy melanoma cells expressing these antigens. MAGE-3 is a cancer-testis antigen, while Melan-A and gp100 are melanocyte differentiation antigens, and NA17 is an intron-derived peptide from the N-acetylglucosaminyltransferase V gene (UniProt P43357, Q16655, P40126). This multi-antigen approach is designed to overcome tumor heterogeneity and prevent immune escape by targeting multiple pathways simultaneously.

Other names
MAGE-3/Melan-A/gp100/NA17-HLA-A2 complexesMulti-epitope melanoma peptide-HLA complexesMelanoma antigen-pulsed PBMCMAGE-A3/MART-1/gp100/NA17-A peptide-MHC complexes
02

Mechanism of action

Induction of tumor-specific cytotoxic T lymphocyte (CTL) responses through the presentation of multiple melanoma-associated epitopes on HLA-A*0201 molecules, facilitating the recognition and lysis of melanoma cells by the immune system.

03

Biological functions

Antigen presentationT-cell activationImmune responseImmune surveillance
04

Disease associations

MelanomaCutaneous melanomaMetastatic melanoma
05

Safety considerations

Vitiligo (depigmentation due to destruction of normal melanocytes)Autoimmune reactions against healthy tissues expressing differentiation antigensInjection site reactionsPotential for immune tolerance or exhaustion
06

Interacting drugs

Autologous dendritic cell vaccine

2 more in the full profile.

07

Biomarkers

HLA-A*0201 allele positivityMAGE-A3 (MAGEA3) expression in tumor tissueMelan-A (MLANA) expression in tumor tissuegp100 (PMEL) expression in tumor tissueIFN-gamma production by T cells (ELISPOT)

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