Target intelligence / Profile preview

B-cell maturation antigen (BCMA)-derived peptide–HLA-A*02:01 complex (BCMA-HLA-A*02:01)

Target
BCMA-HLA-A*02:01
Molecular classification
Peptide-MHC complex, Antigen, Tumor-associated antigen
01

Overview

The B-cell maturation antigen (BCMA)-derived peptide–HLA-A*02:01 complex is a specialized immunological target consisting of a processed fragment of the BCMA protein presented by the Human Leukocyte Antigen (HLA) allele A*02:01 (Source: in-part.com). BCMA is a member of the tumor necrosis factor receptor superfamily and is nearly universally expressed on the surface of malignant plasma cells in multiple myeloma, while being absent from most other healthy tissues (Source: nih.gov). Unlike traditional BCMA-targeted therapies like CAR-T cells or bispecific antibodies that bind to the surface protein, this complex allows for the recognition of BCMA-derived epitopes by T-cell receptors (TCRs) (Source: frontiersin.org). This is particularly useful for developing TCR-engineered T-cell therapies and peptide-based vaccines, such as those utilizing the optimized heteroclitic BCMA72-80 peptide (YLMFLLRKI) (Source: nih.gov). These therapies aim to induce a robust and durable CD8+ cytotoxic T-lymphocyte response against myeloma cells (Source: nih.gov). However, the clinical application of this target is restricted to patients carrying the HLA-A*02:01 allele and faces challenges such as potential antigen escape through the downregulation of BCMA or MHC molecules (Source: frontiersin.org).

Other names
BCMA peptide-MHC complexBCMA-MHC complexBCMA-HLA-A2 complexBCMA72-80-HLA-A*02:01 complex
02

Mechanism of action

Induction of T-cell mediated cytotoxicity through T-cell receptor (TCR) recognition of the peptide-MHC complex.

03

Biological functions

Antigen presentationImmune recognitionT-cell activation
04

Disease associations

Multiple myelomaPlasma cell dyscrasias
05

Safety considerations

HLA restriction (limited to HLA-A*02:01 positive patients)Off-target toxicity due to potential cross-reactivity with similar self-peptidesAntigen escape via downregulation of BCMA or MHC molecules
06

Interacting drugs

Heteroclitic BCMA72-80 peptide (YLMFLLRKI)

2 more in the full profile.

07

Biomarkers

HLA-A*02:01 expressionBCMA expressionSoluble BCMA (sBCMA)

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