Abstract: TH-PO0987
A Protease-Resistant Triple Immunomodulatory Combination Enables Sustained Humoral Immune Control for Xenotransplantation 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
Preformed anti-pig antibodies and antibody-mediated rejection (AMR) remain major barriers to xenotransplantation. Current approaches, including plasma exchange and IVIG, provide only transient antibody reduction and may introduce additional xenoreactive antibodies while reducing exposure of therapeutic antibodies. To address these limitations, we developed a triple-combination regimen consisting of the IgG-degrading enzyme Ricefidase (KJ103), a protease-resistant anti-CD20 antibody (BJ045), and a protease-resistant Fc-silent anti-CD154 antibody (BJ047), designed to maintain activity during systemic IgG degradation.
Methods
BJ045 and BJ047 were engineered to resist Ricefidase-mediated cleavage while preserving immunomodulatory activity. BJ047 was additionally designed with an Fc-silent architecture to minimize Fc-mediated adverse effects, including thrombosis and complement activation. Functional characterization included in vitro assessment of enzymatic resistance, immune inhibitory activity, thrombotic potential, and C1q binding. In vivo pharmacodynamic activity was evaluated in cynomolgus monkeys using KLH immunization models.
Results
BJ045 and BJ047 retained functional activity following Ricefidase exposure in vitro. BJ047 showed no detectable thrombogenic activity or C1q binding while maintaining potent immune inhibitory activity comparable to a benchmark anti-CD154 antibody. In non-human primates, BJ047 achieved near-complete suppression of KLH-induced humoral immune responses. The triple-combination strategy is designed to rapidly eliminate pathogenic IgG through Ricefidase, maintain durable costimulatory blockade via BJ047, and provide sustained B-cell depletion through BJ045 to suppress antibody rebound. Unlike plasma exchange- and IVIG-based approaches, this regimen avoids introduction of exogenous xenoreactive antibodies and preserves therapeutic antibody exposure.
Conclusion
This study supports a novel triple-combination immunomodulatory platform for xenotransplantation desensitization and AMR. By integrating rapid IgG clearance with durable costimulatory blockade and sustained B-cell depletion, this approach may overcome key limitations of plasma exchange- and IVIG-based regimens and enable more durable control of humoral immunity in xenotransplantation.