Inflammatory Bowel Disease Model

Introduction

Inflammatory bowel disease (IBD) is a collective term for long-term (chronic) inflammatory conditions of the digestive tract, with the two most common types being ulcerative colitis and Crohn's disease. The pathogenesis of IBD remains unclear, and studies have shown that multiple factors—including susceptibility genes, the immune system, environmental factors, and gut microbiota—are associated with the development of the disease.

Disease models

The SMOC has long been dedicated to autoimmune disease research and has established a variety of stable IBD disease models based on different induction methods, providing powerful tools for the efficacy evaluation and safety assessment of related drugs.

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Fig.1 4% DSS induced IBD model in C57BL/6 female or male mice. (A) Body weight. (B) DAI Score. 

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Fig.2 4% DSS induced IBD model in C57BL/6 female or male mice. (A) Spleen weight. (B) Colon weight/length. 

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Fig.3. Colon length in 4% DSS induced IBD model.

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Fig.4 Representative histopathology image of each group. 

PBMC in vitro target screening

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Fig1. Donor Screening in vivo.

 

TNBS-induced IBD mouse model and potency data of Anti-TL1A antibody

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Fig2. TNBS induced IBD model in PBMC construction model. (A) DAI score (B) Body weight change.

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Fig3. TNBS induced IBD model in PBMC construction model. (A) DAI score (B) Body weight change (D) Colon weight. (E) Colon length. (F) Colon weight/length.

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Fig4. TNBS induced IBD model in PBMC construction model. (A) Representative HE images. (B) Histopathology score. 


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Fig.1 Efficacy data of Duvakitug in DSS-Induced Chronic IBD Model in hTL1A mice. (A) Model construct schedule; (B) Clinical score; (C) AUC of clinical score.

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Fig.2 Efficacy data of Duvakitug in DSS-Induced Chronic IBD Model in hTL1A mice. (A) Representative photographs of H&E -stained colon sections; (B) colon weight/ colon length; (C)pathology score. 

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Fig.1 In vivo efficacy assessment of RVT3101, Tulisokibart and Duvakitug in the TBNS-induced acute colitis model of HO hTL1A(3) mice.

(A) Body weight change and (B) DAI score in the TBNS-induced acute colitis model of hTL1A(3) mice. In this study, all hTL1A mice were randomly divided into experimental and control cohorts groups on Day -1. The treatment groups received intraperitoneal injections of anti-human TL1A antibody RVT-3101 and Tulisokibart (25mpk), the TL1A inhibitor Duvakitug (25mpk) every three days for a total of two doses. The acute colitis model was established in hTL1A mice by a single intrarectal injection of 1.5% TNBS on Day 0. Body weight and DAI score were recorded daily. (n=6 females per group, 15-16 weeks old, Mean ± SEM, Unpaired t-test, *P<0.05, **P<0.01, ***P<0.0001)

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Fig.2 In vivo efficacy assessment of RVT3101, Tulisokibart and Duvakitug in the TBNS-induced acute colitis model of HO hTL1A(3) mice.

(A) Colon index. (B) Colon photo. On Day 5, all mice were sacrificed, and the isolated colons were subjected to weight and photograph. The results demonstrated that, compared with the control group, treatment groups exhibited a significant amelioration of TBNS-induced acute colitis in hTL1A mice. (n=6 females per group, 15-16 weeks old, Mean ± SEM, Unpaired t-test, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001)

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Fig.3 In vivo efficacy assessment of RVT3101, Tulisokibart and Duvakitug in the TBNS-induced acute colitis model of HO hTL1A(3) mice.

Histopathological evaluation of colon tissues in the TBNS-induced acute colitis of hTL1A(3) mice. On Day 5, all mice were sacrificed, and the isolated colons were subjected to embed in paraffin with HE staining. Treatment with Duvakitug and RVT-3101 significantly improved TBNS-induced acute colitis in hTL1A mice. (n=6 females per group, 15-16 weeks old, Mean ± SEM, Unpaired t-test, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001) 


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Fig.1 In vivo efficacy assessment of RVT3101, Tulisokibart and Duvakitug in the TBNS-induced acute colitis model of hDR3(2)/hTL1A(3) mice. (A) Body weight change; (B) DAI score. 

In this study, all hDR3/hTL1A mice were randomly divided into experimental and control cohorts groups on Day -1. The treatment groups received intraperitoneal injections of anti-human TL1A antibody RVT-3101 and Tulisokibart (25mpk), the TL1A inhibitor Duvakitug (25mpk) every three days for a total of two doses. The acute colitis model was established in hDR3/hTL1A mice by a single intrarectal injection of 1.5% TNBS on Day 0. Body weight and DAI score were recorded daily. (n=3 males and 2 females per group, 6-8 weeks old, Mean ± SEM, Unpaired t-test, *P<0.05, **P<0.01, ***P<0.0001)

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Fig.2 In vivo efficacy assessment of RVT3101, Tulisokibart and Duvakitug in the TBNS-induced acute colitis model of hDR3(2)/hTL1A(3) mice. (A) Colon index; (B) Colon photo.

On Day 5, all mice were sacrificed, and the isolated colons were subjected to weight and photograph. The results demonstrated that, compared with the control group, treatment groups exhibited a significant amelioration of TBNS-induced acute colitis in hDR3/hTL1A mice. (n=3 males and 2 females per group, 6-8 weeks old, Mean ± SEM, Unpaired t-test, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001)

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