TNF receptor superfamily member 17
TNF receptor superfamily member 17
Overview
TNF receptor superfamily member 17 (TNFRSF17), commonly known as B-cell maturation antigen (BCMA), is a transmembrane glycoprotein receptor encoded by the TNFRSF17 gene and belonging to the tumor necrosis factor receptor superfamily. It is selectively expressed on terminally differentiated B-lineage cells, including memory B cells, plasmablasts, and long-lived plasma cells, where it mediates survival and proliferation signals primarily through its ligands APRIL (a proliferation-inducing ligand) and BAFF (B-cell activating factor). Under homeostatic conditions, BCMA signaling supports the maintenance of the long-lived plasma cell compartment in the bone marrow.
BCMA's highly restricted expression pattern — largely absent from naive B cells and non-hematopoietic tissues — makes it an attractive and selective therapeutic target. Its expression is markedly upregulated on malignant plasma cells in multiple myeloma, enabling targeting strategies that spare most healthy tissues. A soluble form of BCMA (sBCMA) is shed from cell surfaces by gamma-secretase cleavage and is detectable in serum, where it can serve as a pharmacodynamic and disease-monitoring biomarker. The convergence of BCMA's biology with the clinical urgency of relapsed and refractory multiple myeloma has driven an extraordinary expansion of BCMA-directed therapeutic modalities, including antibody-drug conjugates, bispecific T-cell engagers, and chimeric antigen receptor (CAR) T-cell therapies.
Focus of Latest Publications
Recent publications have established B-cell maturation antigen (TNFRSF17/BCMA) as a high-priority therapeutic target for multiple myeloma and related hematologic malignancies. Multiple immunotherapeutic modalities targeting BCMA have entered clinical development, including bispecific T-cell engagers, chimeric antigen receptor (CAR) T-cell therapies, bispecific antibodies, and antibody-drug conjugates. The clinical data consistently demonstrate deep and durable responses: durcabtagene autoleucel, a BCMA-directed CAR T therapy, achieved a 98% overall response rate with 55% stringent complete response in relapsed/refractory multiple myeloma (r/r MM), while ciltacabtagene autoleucel demonstrated superior progression-free and overall survival compared with standard of care in earlier-line settings. Belantamab mafodotin, a BCMA-targeting antibody-drug conjugate, combined with carfilzomib, lenalidomide, and dexamethasone showed 89.5% overall response rates with manageable toxicity despite grade ≥3 keratopathy in approximately one-third of patients.
The breadth of BCMA-directed approaches now extends beyond traditional monotherapies. Dual-targeting CAR T strategies such as AZD0120, which simultaneously engages BCMA and CD19, have shown promise in older patients with newly diagnosed multiple myeloma, achieving minimal residual disease negativity in all evaluable patients with a manageable safety profile. Mechanistic studies reveal that endogenous CD28 signaling on CAR T cells targeting BCMA enhances persistent anti-tumor activity through reprogramming of mitochondrial metabolism and modulation of the tumor microenvironment. Biomarker development has progressed in parallel, with validated liquid chromatography–mass spectrometry methods now enabling quantification of soluble BCMA as a potential marker of disease burden and target-mediated drug disposition, supporting clinical decision-making.
Emerging evidence indicates that BCMA-targeted therapies may extend beyond hematologic malignancies. A case series documented two patients with treatment-refractory chronic immune-mediated peripheral nerve myelinopathies who achieved rapid clinical improvement and neurological recovery following treatment with teclistamab, a bispecific T-cell engager depleting BCMA-positive plasma cells, suggesting therapeutic potential in autoimmune conditions. Additionally, novel imaging approaches have been developed to monitor BCMA CAR-positive malignancies; a [68Ga]Ga-BCMA-based PET/MR probe demonstrated superior imaging contrast and stronger correlation with tumor burden compared to conventional [18F]FDG imaging, offering improved tools for non-invasive surveillance of CAR-T therapies.
Key Publications
- Jun Therapeutic effect of T-cell engager in two patients with autoimmune neuropathy. (Nature communications, 2026, PMID 42218153): "The bispecific T-cell engager (BiTE) teclistamab depletes B-cell Maturation Antigen (BCMA) positive late-stage B- cells and plasma cells by engaging T-cells."
- Jun Biomedical publication details. (PubMed Database, 2026, PMID 42207978)
- May Efficacy and safety of durcabtagene autoleucel in a phase 1 trial for patients with relapsed/refractory multiple myeloma. (Science translational medicine, 2026, PMID 42202046): "Traditional manufacturing of B cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T cell therapies is prolonged, leading to reduced patient access, T cell exhaustion, and consequently limiting therapeutic efficacy."
- May Standard-of-care ciltacabtagene autoleucel in earlier versus later lines of therapy for relapsed or refractory multiple myeloma: a nationwide registry analysis. (Journal of hematology & oncology, 2026, PMID 42163304): "Ciltacabtagene autoleucel (cilta-cel) is a BCMA-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed or refractory multiple myeloma (RRMM)."
- Jun Efficacy and safety of elranatamab in patients with relapsed or refractory multiple myeloma: A US subgroup analysis from MagnetisMM-3. (Cancer, 2026, PMID 42159085): "Elranatamab, approved for relapsed or refractory multiple myeloma, demonstrated deep, durable responses and manageable safety in patients without prior B-cell maturation antigen (BCMA)-directed therapy (BCMA-naive) in MagnetisMM-3 (NCT04649359)."
- May Targeting CD74 may mitigate immune-escape features and enhance BCMA CAR-T activity in preclinical models of relapsed/refractory multiple myeloma. (Journal for immunotherapy of cancer, 2026, PMID 42134899): "B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy has demonstrated substantial clinical benefit in relapsed/refractory multiple myeloma (R/R MM)."
- Jun BCMA/CD19 dual-targeting CAR T-cell therapy in older patients with newly diagnosed multiple myeloma: a phase 1 study. (Blood advances, 2026, PMID 41925575): "GC012F, now renamed AZD0120, is an autologous B-cell maturation antigen and CD19 dual-targeting chimeric antigen receptor (CAR) T-cell product manufactured on the FasTCAR platform."
- May Quantification of total soluble BCMA from human serum in the presence of natural and therapeutic ligands by LC-MS/MS. (Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, 2026, PMID 41880915): "B-cell maturation antigen is highly expressed in myeloma cells and is an attractive target for multiple myeloma (MM) therapies."
- May Belantamab mafodotin, carfilzomib, lenalidomide, and dexamethasone for relapsed or refractory multiple myeloma. (Blood advances, 2026, PMID 41719502): "Belantamab mafodotin (belamaf), an antibody-drug conjugate targeting B-cell maturation antigen, has demonstrated single-agent activity in relapsed/refractory multiple myeloma (RRMM) but is associated with ocular toxicity."
- May Endogenous CD28 Drives the Persistent Activity of CAR T Cells in Myeloma and Lymphoma Models. (Blood cancer discovery, 2026, PMID 41627211): "yet most patients treated with BCMA-targeted CAR T cells experience disease relapse."