NLRP3 inflammasome inhibition by the novel bispecific antibody inflamab inhibits atherosclerosis in apolipoprotein E-deficient mice

L. Delfos, M.A.C. Depuydt, A. Foks, M. Bernabe Kleijn, J. Kuiper, M. Chemaly, A. Peace, V. Mcgilligan, I. Bot

Research output: Contribution to journalMeeting Abstractpeer-review


Background and Aims: Cardiovascular disease remains the most common cause of mortality worldwide, which is attributable to the underlying chronic inflammatory condition atherosclerosis. The NLRP3 inflammasome is involved in regulating multiple inflammatory diseases, including atherosclerosis. Here, we aimed to determine the efficacy of the novel bispecific antibody InflamAb, designed to target the NLRP3 inflammasome, in inhibiting atherosclerosis.
Methods: We treated western-type diet fed male apoE-/- mice for 3x per week with 100 μg InflamAb or isotype control antibody (n=11-13) during collar-induced atherosclerosis development for 4 weeks, after which atherosclerosis in the carotid artery was analyzed.
Results: Exposure of bone marrow derived macrophages to 25 ng/mL InflamAb prevented the LPA+Alum induced IL-1β release (P<0.05). In vivo, administration of InflamAb significantly reduced circulating IL-1β at 4 hours after LPS injection in western-type diet fed apoE-/- mice (P<0.05). InflamAb treatment significantly inhibited atherosclerotic plaque development from 59±8*103 μm2 in control mice to 36±5*103 μm2 (P<0.05), which was accompanied by a reduction in relative macrophage (control: 36±2% versus InflamAb: 28±3%, P<0.05) and necrotic core content (control: 16±2% versus InflamAb: 8±1%, P<0.05). In apoE-/-mice with established atherosclerosis, InflamAb treatment for 6 weeks did not affect lesion size, but significantly reduced relative macrophage (control: 48±2% versus InflamAb: 42±2%, P<0.05) and necrotic core content (control: 21±1% versus InflamAb: 18±1%, P<0.05) compared to controls, suggesting that InflamAb treatment improved advanced plaque stability.
Conclusions: We here show that inhibition of the NLRP3 inflammasome by the bispecific antibody InflamAb shows promising efficacy in inhibiting atherosclerotic plaque development and destabilization.
Original languageEnglish
Pages (from-to)S2
Issue numberSupplement 1
Publication statusPublished online - 29 Aug 2023


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