Target intelligence / Profile preview

Marginal zone B and B1 cell-specific protein (MZB1) peptide-HLA-A*02 complex (MZB1/HLA-A*02)

Target
MZB1/HLA-A*02
Molecular classification
Peptide-MHC complex, Antigen, Tumor-associated antigen (TAA)
01

Overview

The MZB1-derived peptide presented by HLA-A*02 is a specific peptide-major histocompatibility complex (pMHC) target primarily utilized in the development of T-cell receptor (TCR)-based immunotherapies. Marginal zone B and B1 cell-specific protein (MZB1) is an endoplasmic reticulum-resident chaperone that plays a critical role in the assembly and secretion of immunoglobulin M (IgM) and is highly expressed in plasma cells and their malignant counterparts. In diseases like Multiple Myeloma, MZB1 is significantly overexpressed, making its HLA-presented peptides attractive targets for redirected T-cell therapies. The HLA-A*02 allele is one of the most common MHC Class I molecules in the human population, providing a broad platform for therapeutic application. Drugs targeting this complex, such as TCR-engineered T cells, work by specifically recognizing the peptide-HLA structure on the surface of cancer cells, triggering a cytotoxic immune response. However, because MZB1 is also expressed in healthy plasma cells, therapeutic strategies must carefully manage the risk of B-cell aplasia and other on-target off-tumor effects.

Other names
MZB1-HLA-A2 complexMZB1 peptide-MHC complexpMHC (MZB1/HLA-A*02)MEDA-7 peptide-HLA complexpMHC complex of MZB1-derived peptide and HLA-A*02
02

Mechanism of action

T-cell receptor (TCR) mediated recognition leading to T-cell activation and directed cytotoxicity against cells presenting the MZB1 peptide on HLA-A*02.

03

Biological functions

Antigen presentationImmune recognitionT-cell activationProtein folding and secretion (MZB1 parent protein)IgM assembly (MZB1 parent protein)
04

Disease associations

Multiple MyelomaB-cell malignanciesPlasma cell dyscrasiasSystemic lupus erythematosus
05

Safety considerations

On-target off-tumor toxicity (targeting normal plasma cells)Cross-reactivity with similar self-peptidesCytokine release syndrome (CRS)Neurotoxicity associated with CAR-T/TCR-T therapies
06

Interacting drugs

MZB1-specific TCR-T cells

2 more in the full profile.

07

Biomarkers

MZB1 protein expressionHLA-A*02:01 genotypeMZB1 mRNA levels

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