Abstract: FR-PO0803
B-Cell-Activating Factor Ligand-Based Chimeric Antigen Receptor-T Cells Preferentially Deplete Plasmablasts and Transitional B Cells While Preserving Naïve B Cells in Membranous Nephropathy
Session Information
- Glomerular Diseases: Practice and New Concepts Shaping Modern Care
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Chung, Edmund YM, Children's Hospital at Westmead Centre for Kidney Research, Westmead, New South Wales, Australia
- Gowrishankar, Kavitha, The University of Sydney, Sydney, New South Wales, Australia
- Shaw, Karli I., Children's Hospital at Westmead Centre for Kidney Research, Westmead, New South Wales, Australia
- Wang, Yuan Min, Children's Hospital at Westmead Centre for Kidney Research, Westmead, New South Wales, Australia
- Halpin, Joshua Colin, Children's Cancer Research Unit, Westmead, New South Wales, Australia
- Rigterink, Jennifer, Children's Hospital at Westmead Centre for Kidney Research, Westmead, New South Wales, Australia
- Ronning, Emily, Children's Hospital at Westmead Centre for Kidney Research, Westmead, New South Wales, Australia
- Keung, Karen L., Prince of Wales Hospital and Community Health Services, Randwick, New South Wales, Australia
- McCarthy, Hugh J., Children's Hospital at Westmead Centre for Kidney Research, Westmead, New South Wales, Australia
- Alexander, Stephen I., Children's Hospital at Westmead Centre for Kidney Research, Westmead, New South Wales, Australia
Background
B cell-activating factor (BAFF) is crucial for B-cell survival and maturation into plasma cells. BAFF ligand-based chimeric antigen receptor (CAR) T-cells are an attractive strategy to target the three cognate receptors for BAFF (BAFF-R, TACI, and BCMA), mostly expressed on mature B-cells and plasma cells, which are implicated in membranous nephropathy (MN).
Methods
We generated a truncated BAFF trimeric CAR T-cell using the non-viral PiggyBac transposon system. Cytotoxicity against Raji B-cells and HEK293T cells were evaluated using the Calcein assay and intracellular cytokine release was assessed by flow cytometry. Peripheral blood mononuclear cells in patients with MN and healthy controls were co-cultured with BAFF CAR T-cells or unmodified T-cells and B-cell subsets were assessed by flow cytometry.
Results
BAFF CAR T-cells demonstrated increased cytotoxicity against Raji B-cells compared to unmodified T-cells but not against a negative cell line (HEK293T cells) (Figure 1A). Co-culture with Raji B-cells increased degranulation (CD107a) and proinflammatory cytokines (IFN-γ, TNF-α, and IL-2) for BAFF CAR T-cells compared to unmodified T-cells (Figure 1B). B-cells in patients with MN exhibited increased TACI and BCMA compared to healthy controls (Figure 2A). In patients with MN, BAFF CAR T-cells eliminated transitional B-cells and plasmablasts but naïve B-cells were preserved compared to unmodified T-cells (Figure 2B).
Conclusion
BAFF CAR T-cells preferentially eliminated plasmablasts and transitional B-cells while preserving naïve B-cells in patients with MN, which may be a targeted therapy against activated B-cells that cause autoantibody production in MN.
Acknowledgment
The authors thank Dr Amanda Tan, Ms Sayali Gore for their technical assistance with CAR T-cell experiments, and A/Prof Kenneth Micklewaite for technical assistance with BAFF CAR T-cell design.