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Synovial sarcoma, X breakpoint 2 peptide (41-49) presented by HLA-A*02:01 (SSX2(41-49)/HLA-A*02:01)

Target
SSX2(41-49)/HLA-A*02:01
Molecular classification
Peptide-MHC complex, Antigenic peptide, Cancer-testis antigen
01

Overview

The SSX2 peptide 41-49/HLA-A*02:01 complex is a specific peptide-major histocompatibility complex (pMHC) target used in cancer immunotherapy. SSX2 (Synovial Sarcoma, X breakpoint 2), also known as HOM-MEL-40, is a member of the cancer-testis antigen (CTA) family, which is characterized by high expression in various malignancies but restricted expression in the testis and other immune-privileged normal tissues [1, 7, 11]. The specific nonameric peptide KASEKIFYV (residues 41-49) is processed endogenously and presented on the cell surface by the HLA-A*02:01 molecule, making it an immunodominant epitope for CD8+ T cells [1, 3, 8]. This complex has become a focal point for the development of adoptive cellular therapies, including T-cell receptor (TCR) engineered T cells and TCR-like chimeric antigen receptor (CAR) T cells, which are designed to recognize and lyse HLA-A*02:01-positive, SSX2-expressing tumor cells [4, 5]. Clinical and preclinical studies have explored its utility in treating a broad range of cancers, including synovial sarcoma, melanoma, and acute myeloid leukemia [1, 4, 12].

Other names
SSX2 peptide 41-49/HLA-A*0201 complexKASEKIFYV/HLA-A*02:01 complexSSX-2 p41-49/HLA-A2Synovial sarcoma X breakpoint 2 (41-49) epitopeHOM-MEL-40 peptide 41-49
02

Mechanism of action

T-cell receptor (TCR) or TCR-like chimeric antigen receptor (CAR) binding to the peptide-MHC complex on tumor cells, leading to targeted T-cell-mediated cytotoxicity and interferon-gamma release.

03

Biological functions

Antigen presentationImmune surveillanceT-cell activationLymphocyte proliferation
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Disease associations

Synovial sarcomaMelanomaAcute myeloid leukemiaProstate cancerHepatocellular carcinomaMultiple myeloma
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Safety considerations

Off-target toxicity (cross-reactivity with similar SSX family peptides)Cytokine release syndrome (CRS)NeurotoxicityOn-target off-tumor activity in immune-privileged tissues
06

Interacting drugs

ADP-A2SSX

3 more in the full profile.

07

Biomarkers

SSX2 mRNA expressionSSX2 protein expression (IHC)HLA-A*02:01 genotype

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