Abstract: TH-PO0986
Durable B-Cell Depletion After Ricefidase-Mediated IgG Cleavage Using a Protease-Resistant Anti-CD20 Antibody for Transplant Desensitization and Antibody-Mediated Rejection
Session Information
- Transplantation: Basic - Immune Biology, Tissue Injury, and Emerging Technologies
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2001 Transplantation: Basic
Authors
- Yan, Chaoyue, Shanghai Bao Pharmaceuticals Co., Ltd., Shanghai, China
- Xu, Yunxia, Shanghai Bao Pharmaceuticals Co., Ltd., Shanghai, China
- Zhu, Zhen, Shanghai Bao Pharmaceuticals Co., Ltd., Shanghai, China
- Liu, Yanjun, Shanghai Bao Pharmaceuticals Co., Ltd., Shanghai, China
Background
Pre-transplant sensitization and antibody-mediated rejection (AMR) remain major barriers to successful kidney transplantation. Current treatments, including plasma exchange and rituximab, are limited by incomplete IgG removal, procedural burden, and delayed B-cell depletion. Ricefidase (KJ103) is an IgG-degrading enzyme capable of rapidly eliminating circulating IgG antibodies. However, conventional anti-CD20 antibodies may themselves be cleaved after Ricefidase administration, potentially reducing sustained B-cell suppression. To address this limitation, we developed a protease-resistant anti-CD20 antibody designed to maintain activity in the presence of Ricefidase and support subcutaneous administration.
Methods
The anti-CD20 antibody was engineered to resist Ricefidase-mediated cleavage while preserving effector functions. ADCC, ADCP, direct cell death (DCD), and CDC activities were evaluated in vitro. Pharmacokinetics, tolerability, and pharmacodynamic activity were assessed in cynomolgus monkeys after subcutaneous administration.
Results
The protease-resistant anti-CD20 antibody retained robust ADCC, ADCP, DCD, and CDC activities in vitro. In non-human primates, the subcutaneous formulation showed favorable exposure and good tolerability. Combination treatment with Ricefidase and the protease-resistant anti-CD20 antibody achieved near-complete peripheral B-cell depletion for approximately 70 days despite concurrent systemic IgG degradation, demonstrating durable pharmacodynamic activity. These findings support sustained suppression of donor-specific antibody reconstitution following rapid IgG removal.
Conclusion
Ricefidase combined with a protease-resistant anti-CD20 antibody represents a potential new strategy for transplant desensitization and AMR. By combining rapid pathogenic IgG elimination with prolonged B-cell depletion, this regimen may offer a practical and potentially more effective alternative to plasma exchange plus rituximab. The approach may also have broader applications in acute antibody-mediated autoimmune diseases requiring rapid IgG removal and durable suppression of autoreactive B cells.