ArticleClinical and translational medicine2024
Novel bispecific nanobody mitigates experimental intestinal inflammation in mice by targeting TNF-α and IL-23p19 bioactivities.
Article in Clinical and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 11 citations in OpenAlex.
- A phase 1 study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of PF-07261271 in healthy participants.British journal of clinical pharmacology · 2026Trial
- Engineering and Partial Characterization of an Anti-IL-23/Anti-TNF-α Bispecific Domain Antibody Fused to Human Serum Albumin Domain for Inflammatory Disease Therapy.Applied biochemistry and biotechnology · 2026Article
- The dual balance of the cytokine network: key messengers of immune activation and triggers of cytokine storm.Biomarker research · 2026Review
- Cytotoxic CD4Signal transduction and targeted therapy · 2026Review
- Mechanisms of inflammation in premature ovarian insufficiency and advances in therapeutic studies.Frontiers in immunology · 2026Review
- Noncanonical amino acid-aided synthesis of anti-PD-L1 bispecific nanobody for colon cancer immunotherapy.Communications biology · 2025Article
- Oral microbiota-regulating and inflammation-targeted polymersome-hydrogels for RNAi therapy of ulcerative colitis.Bioactive materials · 2025Article
- Unveiling the new chapter in nanobody engineering: advances in traditional construction and AI-driven optimization.Journal of nanobiotechnology · 2025Review
- Key Interleukins in Inflammatory Bowel Disease-A Review of Recent Studies.International journal of molecular sciences · 2024Review
- Infliximab inhibits TNF-α-dependent activation of the NLRP3/IL-1β pathway in acne inversa.Heliyon · 2024Article
- Novel bispecific nanobody mitigates experimental intestinal inflammation in mice by targeting TNF-α and IL-23p19 bioactivities.Clinical and translational medicine · 2024Article
- Myrrh Essential Oil Improves DSS-Induced Colitis by Modulating the MAPK Signaling Pathway: In vitro and in vivo Studies.Journal of inflammation research · 2024Article
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Authors and funding
17 authors at 8 institutions in 2 countries.
Funding
Abstract
backgroundInflammatory bowel diseases (IBDs) pose significant challenges in terms of treatment non-response, necessitating the development of novel therapeutic approaches. Although biological medicines that target TNF-α (tumour necrosis factor-α) have shown clinical success in some IBD patients, a substantial proportion still fails to respond.
methodsWe designed bispecific nanobodies (BsNbs) with the ability to simultaneously target human macrophage-expressed membrane TNF-α (hmTNF-α) and IL-23. Additionally, we fused the constant region of human IgG1 Fc (hIgG1 Fc) to BsNb to create BsNb-Fc. Our study encompassed in vitro and in vivo characterization of BsNb and BsNb-Fc.
resultsBsNb-Fc exhibited an improved serum half-life, targeting capability and effector function than BsNb. It's demonstrated that BsNb-Fc exhibited superior anti-inflammatory effects compared to the anti-TNF-α mAb (infliximab, IFX) combined with anti-IL-12/IL-23p40 mAb (ustekinumab, UST) by Transwell co-culture assays. Notably, in murine models of acute colitis brought on by 2,4,6-trinitrobenzene sulfonic acid（TNBS) and dextran sulphate sodium (DSS), BsNb-Fc effectively alleviated colitis severity. Additionally, BsNb-Fc outperformed the IFX&UST combination in TNBS-induced colitis, significantly reducing colon inflammation in mice with colitis produced by TNBS and DSS.
conclusionThese findings highlight an enhanced efficacy and improved biostability of BsNb-Fc, suggesting its potential as a promising therapeutic option for IBD patients with insufficient response to TNF-α inhibition. KEY POINTS: A bispecific nanobody (BsNb) was created to target TNF-α and IL-23p19, exhibiting high affinity and remarkable stability. BsNb-Fc inhibited the release of cytokines in CD4+T cells during co-culture experiments. BsNb-Fc effectively alleviated colitis severity in mouse model with acute colitis induced by DSS or TNBS, outperforming the IFX&UST combination.
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