ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2017
Effect of the Anti-C1s Humanized Antibody TNT009 and Its Parental Mouse Variant TNT003 on HLA Antibody-Induced Complement Activation-A Preclinical In Vitro Study.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Evolving Therapeutic Approaches for Treatment of Antibody-Mediated Rejection in Renal Allograft Recipients.Results and problems in cell differentiation · 2026Review
- Torque Teno Virus Control by the Classical Pathway of Complement Activation-A Retrospective Analysis From a First-in-Human Trial Utilizing Sutimlimab.Journal of medical virology · 2024Article
- C1s targeting antibodies inhibit the growth of cutaneous squamous carcinoma cells.Scientific reports · 2024Article
- The Complement System as a Therapeutic Target in Retinal Disease.Medicina (Kaunas, Lithuania) · 2024Review
- Sutimlimab for the Treatment of Cold Agglutinin Disease.HemaSphere · 2023Review
- Aberrant activation of the complement system in renal grafts is mediated by cold storage.American journal of physiology. Renal physiology · 2021Article
- Cold Agglutinin Disease.Clinical hematology international · 2020Review
- Therapeutic Modulation of the Complement System in Kidney Transplantation: Clinical Indications and Emerging Drug Leads.Frontiers in immunology · 2019Review
- Intrarenal Complement System Transcripts in Chronic Antibody-Mediated Rejection and Recurrent IgA Nephropathy in Kidney Transplantation.Frontiers in immunology · 2018Article
- Effect of the Anti-C1s Humanized Antibody TNT009 and Its Parental Mouse Variant TNT003 on HLA Antibody-Induced Complement Activation-A Preclinical In Vitro Study.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2017Article
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12 authors.
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Abstract
The classic pathway (CP) of complement is believed to significantly contribute to alloantibody-mediated transplant injury, and targeted complement inhibition is currently considered to be a promising approach for preventing rejection. Here, we investigated the mode of action and efficacy of the humanized anti-C1s monoclonal antibody TNT009 and its parental mouse variant, TNT003, in preclinical in vitro models of HLA antibody-triggered CP activation. In flow cytometric assays, we measured the attachment of C1 subcomponents and C4/C3 split products (C4b/d, C3b/d) to HLA antigen-coated flow beads or HLA-mismatched aortic endothelial cells and splenic lymphocytes. Anti-C1s antibodies profoundly inhibited C3 activation at concentrations >20 μg/mL, in both solid phase and cellular assays. While C4 activation was also prevented, this was not the case for C1 subcomponent attachment. Analysis of serum samples obtained from 68 sensitized transplant candidates revealed that the potency of inhibition was related to the extent of baseline CP activation. This study demonstrates that anti-C1s antibodies TNT009 and TNT003 are highly effective in blocking HLA antibody-triggered complement activation downstream of C1. Our results provide the foundation for clinical studies designed to investigate the potential of TNT009 in the treatment or prevention of complement-mediated tissue injury in sensitized transplant recipients.
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