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Melanoma-associated antigen 3 243–258 peptide presented by HLA-DP*04 (MAGE-A3(243–258)/HLA-DP*04; MA3/DP4 peptide; sometimes "MAGE-A3 DP4 epitope")

Target
MAGE-A3(243–258)/HLA-DP*04; MA3/DP4 peptide; sometimes "MAGE-A3 DP4 epitope"
Molecular classification
Antigenic peptide (tumor-associated antigen), MHC class II-restricted epitope, Cancer/testis antigen derivative, Immunological target, Receptor ligand (binds HLA-DP*04)
01

Overview

The MAGE-A3 243–258 peptide presented by HLA-DP*04 is a 16-amino acid peptide epitope derived from the melanoma-associated antigen 3 (MAGE-A3) protein. This peptide is efficiently processed and presented by the common HLA-DP*04 (DPB1*0401) allele. It serves as a targetable antigen for CD4+ T cell-based immunotherapies because MAGE-A3 is highly and selectively expressed in various cancers but not in normal tissues (except testes), making it ideal for tumor specificity. Therapeutic strategies focus on engineering T cells with TCRs specific to this epitope, aiming to induce anti-tumor immunity in MAGE-A3 positive, HLA-DP*04 positive patients. Several clinical trials are investigating adoptive transfer of these TCR-modified T cells, with promising preclinical rationale for broad cancer coverage due to the high prevalence of both the antigen and presenting HLA allele in the population[1][2][4][5][3]. Presented on the cell surface by HLA-DP*04, a class II MHC molecule, enabling recognition by CD4+ T cells. The peptide derives from intracellular processing and is loaded onto HLA-DP*04 by both endogenous and exogenous mechanisms[3][6].

Other names
MAGE-A3 DP4 peptideMA3/DP4 epitopeMAGE-A3 243–258 peptideMAGE-A3(243–258)/HLA-DP4 peptideMAGE-A3:243-258 HLA-DP*04-restricted epitope
02

Mechanism of action

Recognition of tumor cells expressing MAGE-A3 by CD4+ T cells, leading to cytokine release, cytolytic activity, and potentially tumor cell death. Adoptive transfer of engineered T cells expressing MAGE-A3 DP4-specific TCRs to augment anti-tumor immunity.

03

Biological functions

Immune response (elicits specific CD4+ T cell responses)Tumor antigen presentation (source for cellular immune recognition in cancer)Mediates fibronectin-controlled progression and metastasis (via full protein expression)Patient selection for immunotherapy trials
04

Disease associations

Cancer (melanoma, non-small cell lung cancer, hepatocellular carcinoma, colon, prostate, breast, myeloma, others)Biomarker for poor prognosis in several tumor types
05

Safety considerations

Off-tumor, on-target toxicity (though MAGE-A3 is not expressed in normal tissues except testes, minimizing the risk of adverse effects)Possible cross-reactivity with the homologous protein MAGE-A6Immune-related adverse events, especially with TCR-based therapiesSuppression of effector responses by CD4+ regulatory T cells recognizing same epitope
06

Interacting drugs

TCR-engineered T cells (T cell receptor gene therapies targeting MAGE-A3 epitope)

2 more in the full profile.

07

Biomarkers

Expression of MAGE-A3 protein in tumorsHLA-DP*04 (DPB1*0401) allele status in patientsFrequency of MAGE-A3-specific T cells in peripheral blood (for ex vivo expansion and monitoring)

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