P717 The use of combination biologic therapy in inflammatory bowel disease: A single tertiary-centre experience

Panaccione, Nicola; Novak, Kerri L.; Seow, Cynthia H.; Devlin, Shane; Lu, Cathy; Heatherington, Joan; Martin, M; Kaplan, Gilaad G.; Panaccione, Remo

doi:10.1093/ecco-jcc/jjy222.841

Cited by 4 publications

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“…17 The therapeutic use of UST and anti-TNF-α antibodies appears to be safe and well-tolerated in IBD patients, although the number of patients involved in the study is limited. [18][19][20] Using bispecific antibodies (BsAbs) to target TNF-α and IL-23p19 simultaneously has emerged as a promising strategy to improve therapeutic efficacy and simplify combinatorial therapy for IBD. 21,22 BsAbs has primarily been used in oncology, [23][24][25][26] recent research has demonstrated that the bispecific antibody Amivantamab exhibits long-lasting and sustained remission in the management of non-small cell lung cancer (NSCLC) with cEGFR mutations, marking a significant breakthrough in cEGFRmutated NSCLC therapy.…”

Section: Schematic Illustration Of Engineering a Bispecific Nanobody-...mentioning

confidence: 99%

“…Among these combinations, we concluded that synergistic effects exist between anti‐IL‐12/23p40 and anti‐TNF‐α agents 17 . The therapeutic use of UST and anti‐TNF‐α antibodies appears to be safe and well‐tolerated in IBD patients, although the number of patients involved in the study is limited 18–20 …”

Section: Introductionmentioning

confidence: 97%

“… 17 The therapeutic use of UST and anti‐TNF‐α antibodies appears to be safe and well‐tolerated in IBD patients, although the number of patients involved in the study is limited. 18 , 19 , 20 …”

Section: Introductionmentioning

confidence: 99%

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Novel bispecific nanobody mitigates experimental intestinal inflammation in mice by targeting TNF‐α and IL‐23p19 bioactivities

Wang,

Kang,

et al. 2024

Clinical & Translational Med

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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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Section: Schematic Illustration Of Engineering a Bispecific Nanobody-...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Novel bispecific nanobody mitigates experimental intestinal inflammation in mice by targeting TNF‐α and IL‐23p19 bioactivities

Wang,

Kang,

et al. 2024

Clinical & Translational Med

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“…In addition, more than 20 case series and reports provide interesting examples of different clinical scenarios45–67 and several retrospective and uncontrolled observations have explored the outcomes of ACT in patients with refractory intestinal disease, concomitant extraintestinal manifestations or IMID (online supplemental table 1).…”

Section: The Current State-of-the-art In Ibdmentioning

confidence: 99%

The future of drug development for inflammatory bowel disease: the need to ACT (advanced combination treatment)

Danese

Solitano

Jairath

et al. 2022

Gut

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Golimumab/steroids/vedolizumab

2019

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P717 The use of combination biologic therapy in inflammatory bowel disease: A single tertiary-centre experience

Cited by 4 publications

References 0 publications

Novel bispecific nanobody mitigates experimental intestinal inflammation in mice by targeting TNF‐α and IL‐23p19 bioactivities

Novel bispecific nanobody mitigates experimental intestinal inflammation in mice by targeting TNF‐α and IL‐23p19 bioactivities

The future of drug development for inflammatory bowel disease: the need to ACT (advanced combination treatment)

Golimumab/steroids/vedolizumab

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