NLRP3 Inflammasome Inhibition by the Novel Bispecific Antibody InflamAb Attenuates Atherosclerosis in Apolipoprotein E–Deficient Mice
The NLRP3 inflammasome contributes to the inflammatory process in atherosclerosis by producing IL-1β. Components of the intracellular NLRP3 inflammasome have been shown to be expressed by macrophages in the atherosclerotic plaque and are a potential therapeutic target. We aimed to determine the efficacy of the novel bispecific antibody InflamAb, designed to target the interleukin-1 receptor type 1 and the NLRP3 inflammasome, in inhibiting atherosclerosis. InflamAb effectively inhibited IL-1β secretion from bone marrow-derived macrophages and reduced circulating IL-1β levels in vivo. Furthermore, InflamAb treatment significantly inhibited atherosclerotic plaque development, accompanied by a reduction in relative macrophage and necrotic core content. InflamAb treatment did not affect the size of established atherosclerotic lesions; however, InflamAb significantly reduced relative macrophage and necrotic core content in these plaques. To conclude, inhibition of the NLRP3 inflammasome by the bispecific antibody InflamAb shows promising efficacy in inhibiting atherosclerotic plaque development and destabilization in Apoe<sup>-/-</sup> mice.
Authors
- Amanda C. Foks (ORCID: https://orcid.org/0000-0002-9747-3458)
- Meredith Gregory‐Ksander (ORCID: https://orcid.org/0000-0002-7193-0032)
- Johan Kuiper (ORCID: https://orcid.org/0000-0001-5834-690X)
- Lucie Delfos (ORCID: https://orcid.org/0000-0003-1018-191X)
- Melody Chemaly (ORCID: https://orcid.org/0000-0001-6211-7595)
- Rebecca C. Coll (ORCID: https://orcid.org/0000-0002-7359-6023)
- Christopher Power (ORCID: https://orcid.org/0000-0002-5131-9711)
- Victoria McGilligan (ORCID: https://orcid.org/0000-0003-1013-3504)
- Aaron Peace (ORCID: https://orcid.org/0000-0001-9556-7509)
- Sophie Coyle
- Marie A.C. Depuydt (ORCID: https://orcid.org/0000-0002-7174-1952)
- Frank H. Schaftenaar (ORCID: https://orcid.org/0000-0001-5742-489X)
- Ilze Bot (ORCID: https://orcid.org/0000-0002-1242-1959)
- Mireia N. A. Bernabé Kleijn (ORCID: https://orcid.org/0000-0001-6027-6154)
- Peter J. van Santbrink
- Pier Pieterszoon Lindenbergh
- C. Costello
Institutions
- Leiden University (NL)
- Massachusetts Eye and Ear Infirmary (US)
- University of Ulster (GB)
- Derry City Council (GB)
- Wellcome Trust Centre for the History of Medicine (GB)
- Western Health and Social Care Trust (GB)
- Centre for Human Drug Research (NL)
- China Power Engineering Consulting Group (China) (CN)
- University College London (GB)
Publication Details
- Journal
- JACC Basic to Translational Science
- Published
- 2025-03-05
- DOI
- https://doi.org/10.1016/j.jacbts.2024.12.012
- Citations
- 4
- Primary Topic
- Inflammasome and immune disorders
- Type
- article
- Field-Weighted Citation Impact
- 3.22
Funders
- Ulster University
- Universiteit Leiden
- Hartstichting