Target intelligence / Profile preview

B-cell-specific transcription coactivator OBF-1 (BOB1) peptide presented by Human Leukocyte Antigen B*07:02 (HLA-B*07:02) (BOB1/HLA-B*07:02)

Target
BOB1/HLA-B*07:02
Molecular classification
Peptide-MHC complex, Antigen, Major Histocompatibility Complex (MHC) Class I
01

Overview

BOB1 (also known as POU2AF1, OBF-1, or OCA-B) is a transcriptional coactivator essential for B-cell development and the formation of germinal centers (6, 10). It is highly and specifically expressed in B-lineage cells and their malignant counterparts, including multiple myeloma and various B-cell lymphomas (1, 7). The BOB1 peptide/HLA-B*07:02 complex is a specific peptide-MHC (pMHC) target where a processed peptide from the intracellular BOB1 protein is presented on the cell surface by the HLA-B*07:02 MHC class I molecule (1, 3). This complex is recognized by specific T-cell receptors (TCRs), such as the 4G11 clone, making it a promising target for adoptive T-cell therapies (TCR-T) (1, 9). Because BOB1 is an intracellular protein, it cannot be targeted by standard CAR-T cells or antibodies, but its presentation as a pMHC complex allows for highly specific immune targeting of B-cell malignancies (4, 9). Therapeutic strategies targeting this complex aim to provide high specificity for B-cell malignancies while sparing non-hematopoietic tissues (1, 5). Clinical development focuses on treating patients with relapsed or refractory B-cell cancers who express the HLA-B*07:02 allele (3, 8). Potential challenges include B-cell aplasia due to the expression of BOB1 in healthy B-cells and the requirement for specific HLA matching in patients (1, 9).

Other names
POU2AF1 peptide/HLA-B*07:02OBF-1 peptide/HLA-B*07:02OCA-B peptide/HLA-B*07:02BOB.1 peptide/HLA-B*07:02BOB1_44/HLA-B*07:02
02

Mechanism of action

T-cell mediated cytotoxicity via TCR-mediated recognition of the peptide-MHC complex

03

Biological functions

Antigen presentationImmune recognitionT-cell activationB-cell development
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Disease associations

Multiple MyelomaChronic Lymphocytic LeukemiaMantle Cell LymphomaAcute Lymphoblastic LeukemiaB-cell Lymphoma
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Safety considerations

B-cell aplasiaOn-target off-tumor toxicity to healthy B-cellsPotential cross-reactivity with other HLA-peptide complexes
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Interacting drugs

BOB1-specific TCR-engineered T cells

1 more in the full profile.

07

Biomarkers

HLA-B*07:02 expressionBOB1 (POU2AF1) expression

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