open access

Ahead of print
Original paper
Submitted: 2021-06-28
Accepted: 2021-09-01
Published online: 2021-10-06
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Immunotherapy with a biologically active ICAM-1 mAb and an siRNA targeting TSHR in a BALB/c mouse model of Graves’ disease

Xuan Wang, Wei Liu1, Zhongying Rui, Wei Zheng, Jian Tan, Ning Li, Yang Yu
DOI: 10.5603/EP.a2021.0087
·
Pubmed: 34647608
Affiliations
  1. Department of Otolaryngology Head and Neck Surgery, Tianjin Fourth Central Hospital

open access

Ahead of print
Original Paper
Submitted: 2021-06-28
Accepted: 2021-09-01
Published online: 2021-10-06

Abstract

Objective To study targeted therapies using a biologically active monoclonal antibody against intracellular adhesion molecule-1 (ICAM-1 mAb) and an siRNA targeting thyroid-stimulating hormone (TSH) receptor (TSHR) in a BALB/c mouse model of Graves’ disease (GD). Methods An improved method for establishing a stable model of GD in BALB/c mice was developed by immunization with pcDNA 3.1/TSHR 289 and electroporation (EP). The mice in which GD was successfully established were divided into a nontreated control group, which was treated with continuous immunization, and treated groups, which were treated with the siRNA and ICAM-1 mAb. Normal mice were included as a blank group. These groups were used to compare the effects of treatment with the ICAM-1 mAb and siRNA. Results The two novel treatments markedly improved weight loss, serum thyroxine (T4) levels, thyroid-stimulating hormone antibody (TSAb) levels, thyroid-stimulating blocking antibody (TSBAb) levels and thyroid uptake of 99mTcO4 in GD model mice. Compared with the siRNA treatment, treatment with the ICAM-1 mAb produced more obvious benefits. The differences in the posttreatment indexes between the two treatment groups were statistically significant (P<0.05). Conclusions These preliminary data suggest that both the biologically active ICAM-1 mAb and the siRNA targeting TSHR were effective. The ICAM-1 mAb exerted a better therapeutic effect than the siRNA targeting TSHR. Both treatments showed potential efficacy as novel treatments for GD and may therefore represent therapeutic options in addition to the existing drugs or interventions.

Abstract

Objective To study targeted therapies using a biologically active monoclonal antibody against intracellular adhesion molecule-1 (ICAM-1 mAb) and an siRNA targeting thyroid-stimulating hormone (TSH) receptor (TSHR) in a BALB/c mouse model of Graves’ disease (GD). Methods An improved method for establishing a stable model of GD in BALB/c mice was developed by immunization with pcDNA 3.1/TSHR 289 and electroporation (EP). The mice in which GD was successfully established were divided into a nontreated control group, which was treated with continuous immunization, and treated groups, which were treated with the siRNA and ICAM-1 mAb. Normal mice were included as a blank group. These groups were used to compare the effects of treatment with the ICAM-1 mAb and siRNA. Results The two novel treatments markedly improved weight loss, serum thyroxine (T4) levels, thyroid-stimulating hormone antibody (TSAb) levels, thyroid-stimulating blocking antibody (TSBAb) levels and thyroid uptake of 99mTcO4 in GD model mice. Compared with the siRNA treatment, treatment with the ICAM-1 mAb produced more obvious benefits. The differences in the posttreatment indexes between the two treatment groups were statistically significant (P<0.05). Conclusions These preliminary data suggest that both the biologically active ICAM-1 mAb and the siRNA targeting TSHR were effective. The ICAM-1 mAb exerted a better therapeutic effect than the siRNA targeting TSHR. Both treatments showed potential efficacy as novel treatments for GD and may therefore represent therapeutic options in addition to the existing drugs or interventions.

Get Citation

Keywords

Graves’ disease, Graves’ ophthalmopathy, TSHR, siRNA, monoclonal antibody, ICAM-1

About this article
Title

Immunotherapy with a biologically active ICAM-1 mAb and an siRNA targeting TSHR in a BALB/c mouse model of Graves’ disease

Journal

Endokrynologia Polska

Issue

Ahead of print

Article type

Original paper

Published online

2021-10-06

DOI

10.5603/EP.a2021.0087

Pubmed

34647608

Keywords

Graves’ disease
Graves’ ophthalmopathy
TSHR
siRNA
monoclonal antibody
ICAM-1

Authors

Xuan Wang
Wei Liu
Zhongying Rui
Wei Zheng
Jian Tan
Ning Li
Yang Yu

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