Kidney Week

Abstract: SA-PO720

Therapeutic Targeting of Antibody-Secreting Cells for the Treatment of Autoimmune 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

• Eggers, Marie, University Medical Center Hamburg-Eppendorf, III. Department of Medicine, Hamburg, Germany

Marie Eggers, DrMed

• Schaffrath, Alessa Zoe, University Medical Center Hamburg-Eppendorf, III. Department of Medicine, Hamburg, Germany

Alessa Zoe Schaffrath, MSc

• Eden, Thomas, University Medical Center Hamburg-Eppendorf, Institute of Immunology, Hamburg, Germany

Thomas Eden, PhD

• Huang, Ming, University Medical Center Hamburg-Eppendorf, III. Department of Medicine, Hamburg, Germany

Ming Huang, PhD

• Tode, Natalie, University Medical Center Hamburg-Eppendorf, Institute of Immunology, Hamburg, Germany

Natalie Tode

• Lucas, Renke, University Medical Center Hamburg-Eppendorf, III. Department of Medicine, Hamburg, Germany

Renke Lucas

• Menzel, Stephan, University Medical Center Hamburg-Eppendorf, Institute of Immunology, Hamburg, Germany

Stephan Menzel, PhD

• Koch-Nolte, Friedrich, University Medical Center Hamburg-Eppendorf, Institute of Immunology, Hamburg, Germany

Friedrich Koch-Nolte

• Tomas, Nicola M., University Medical Center Hamburg-Eppendorf, III. Department of Medicine, Hamburg, Germany

Nicola M. Tomas, MD

Background

Antibody-secreting cells (ASCs) are the main source of antibodies and represent an important therapeutic target in antibody-mediated autoimmune diseases. However, molecular targets suitable for the elimination of pathogenic ASCs are sparse. The aim of this study was the identification and evaluation of novel ASC targets for the treatment of antibody-mediated disease.

Methods

We used available cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) datasets to identify surface molecules with high specificity for ASCs. We then generated nanobody-based heavy chain antibodies (hcAbs) against the identified target and tested their cytotoxic effects in vitro, ex vivo and in vivo. We further used a model of experimental autoimmune membranous nephropathy (EAMN) to evaluate the therapeutic potential of this treatment.

Results

We identified a new potential therapeutic target protein with high membrane expression on both human and murine ASCs. In vitro and ex vivo, hcAbs against this target protein mediated potent cellular lysis of human and murine plasma and myeloma cells. Application of these hcAbs in mice induced a strong depletion of ASCs in bone marrow and spleen. Finally, anti-target protein hcAb treatment strongly reduced the levels of antigen-specific antibodies as well as the degree of podocyte damage and improved clinical outcome in the EAMN disease model.

Conclusion

Our study introduces a promising new target protein for the depletion of ASCs in autoimmune diseases. Considering the global burden of severe autoimmune diseases, further investigation of this potential therapeutic strategy is warranted.

Funding

• Government Support – Non-U.S.