Abstract: SA-PO721
Felzartamab Selectively and Potently Targets CD38+ Antibody-Secreting Cells from Patients with Immune-Mediated Kidney Diseases
Session Information
- Glomerular Diseases: Therapeutic Strategies
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Delfino, Tess Arenzana, Human Immunology Biosciences Inc, South San Francisco, California, United States
- Ilieva, Kristina M., MorphoSys AG, Planegg, Bayern, Germany
- Landgraf, Karin, MorphoSys AG, Planegg, Bayern, Germany
- Boxhammer, Rainer, MorphoSys AG, Planegg, Bayern, Germany
- Steidl, Stefan, MorphoSys AG, Planegg, Bayern, Germany
- Flesher, Donna, Human Immunology Biosciences Inc, South San Francisco, California, United States
Background
CD38+ antibody secreting cells (ASC) such as plasmablasts and plasma cells have been implicated in the pathology of many immune-mediated diseases (IMD). Variability in the efficacy of therapies that target earlier B lineage cells in IMD highlights the need to selectively target the pathogenic cellular drivers of disease. Felzartamab (felza) is a fully human monoclonal antibody that binds to CD38 and has the potential to selectively deplete CD38+ ASC that contribute to IMD through secretion of pathogenic antibodies.
Methods
Flow cytometry based CD38 quantification was evaluated on immune cells from peripheral blood, bone marrow, and in vitro differentiated healthy donor and IMD patient ASC. Depletion of ASC after treatment with felza was assessed in an antibody-dependent cell cytotoxicity (ADCC) assay in vitro and in NSG-SGM3 mice engrafted with human CD34+ cord blood cells in vivo.
Results
CD38 is highly expressed on ASC and other cellular drivers of IMD in peripheral blood, bone marrow, and in vitro differentiated ASC from healthy and IMD donors. Felza demonstrated potent ADCC activity on in vitro differentiated ASC from healthy donors and IMD patients with Membranous Nephropathy (MN) and IgA Nephropathy (IgAN) (Figure 1), while sparing earlier B lineage cells. Furthermore, felza treatment reduced spleen and bone marrow CD38+ ASC and human immunoglobulin titers in engrafted humanized NSG-SGM3 mice, suggesting depletion activity in vivo.
Conclusion
These in vitro and in vivo proof of concept studies highlight the capacity of felza to selectively deplete CD38+ ASC, suggesting the potential for clinical utility in antibody-driven IMD. Clinical trials assessing the safety and efficacy of felza in immune-mediated kidney diseases including MN, IgAN, antibody-mediated kidney rejection and lupus nephritis are currently ongoing.
Funding
- Commercial Support – Human Immunology Biosciences, Inc