ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2015
An Anti-C1s Monoclonal, TNT003, Inhibits Complement Activation Induced by Antibodies Against HLA.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- A Randomized, First-in-Human, Healthy Volunteer Trial of sutimlimab, a Humanized Antibody for the Specific Inhibition of the Classical Complement Pathway.Clinical pharmacology and therapeutics · 2018Trial
- Blockade of HLA Antibody-Triggered Classical Complement Activation in Sera From Subjects Dosed With the Anti-C1s Monoclonal Antibody TNT009-Results from a Randomized First-in-Human Phase 1 Trial.Transplantation · 2017Trial
- Interrogating post-transplant donor HLA-specific antibody characteristics and effector functions using clinical bead assays.Human immunology · 2024Article
- Complement C1s as a diagnostic marker and therapeutic target: Progress and propective.Frontiers in immunology · 2022Review
- B Cell Immunity in Lung Transplant Rejection - Effector Mechanisms and Therapeutic Implications.Frontiers in immunology · 2022Review
- Aberrant activation of the complement system in renal grafts is mediated by cold storage.American journal of physiology. Renal physiology · 2021Article
- C1s Inhibition by BIVV009 (Sutimlimab) Prevents Complement-Enhanced Activation of Autoimmune Human B Cells In Vitro.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Therapeutic Modulation of the Complement System in Kidney Transplantation: Clinical Indications and Emerging Drug Leads.Frontiers in immunology · 2019Review
- Understanding the Correlation Between DSA, Complement Activation, and Antibody-Mediated Rejection in Heart Transplant Recipients.Transplantation · 2018Article
- Donor-specific HLA antibody-mediated complement activation is a significant indicator of antibody-mediated rejection and poor long-term graft outcome during lung transplantation: a single center cohort study.Transplant international : official journal of the European Society for Organ Transplantation · 2018Observational
- Innate networking: Thrombotic microangiopathy, the activation of coagulation and complement in the sensitized kidney transplant recipient.Transplantation reviews (Orlando, Fla.) · 2018Review
- The clinical implications of the unique glomerular complement deposition pattern in transplant glomerulopathy.Journal of nephrology · 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
- Complement-Mediated Enhancement of Monocyte Adhesion to Endothelial Cells by HLA Antibodies, and Blockade by a Specific Inhibitor of the Classical Complement Cascade, TNT003.Transplantation · 2017Article
- Recent advances in allograft vasculopathy.Current opinion in organ transplantation · 2017Review
- Not All Antibodies Are Created Equal: Factors That Influence Antibody Mediated Rejection.Journal of immunology research · 2017Review
- Novel Evasion Mechanisms of the Classical Complement Pathway.Journal of immunology (Baltimore, Md. : 1950) · 2016Review
- Innate immune mechanisms in transplant allograft vasculopathy.Current opinion in organ transplantation · 2016Review
- Uncoupling complement C1s activation from C1q binding in apoptotic cell phagocytosis and immunosuppressive capacity.Clinical immunology (Orlando, Fla.) · 2016Article
- SALO, a novel classical pathway complement inhibitor from saliva of the sand fly Lutzomyia longipalpis.Scientific reports · 2016Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Antibody-mediated rejection (AMR) of solid organ transplants (SOT) is characterized by damage triggered by donor-specific antibodies (DSA) binding donor Class I and II HLA (HLA-I and HLA-II) expressed on endothelial cells. While F(ab')2 portions of DSA cause cellular activation and proliferation, Fc regions activate the classical complement cascade, resulting in complement deposition and leukocyte recruitment, both hallmark features of AMR. We characterized the ability of an anti-C1s monoclonal antibody, TNT003, to inhibit HLA antibody (HLA-Ab)-induced complement activation. Complement deposition induced by HLA-Ab was evaluated using novel cell- and bead-based assays. Human aortic endothelial cells (HAEC) were cultured with HLA-Ab and human complement; production of activated complement proteins was measured by flow cytometry. Additionally, C3d deposition was measured on single antigen beads (SAB) mixed with HLA-Ab and human complement. TNT003 inhibited HLA-Ab mediated complement deposition on HAEC in a concentration-dependent manner; C3a, C4a and C5a anaphylatoxin production was also diminished by TNT003. Finally, TNT003 blocked C3d deposition induced by Class I (HLAI-Ab)- and Class II (HLAII-Ab)-specific antibodies on SAB. These data suggest TNT003 may be useful for modulating the effects of DSA, as TNT003 inhibits complement deposition and split product formation generated by HLA-I/II-Ab in vitro.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.