Investigational therapies targeting CD3 for prevention and treatment of type 1 diabetes. (2nd December 2021)

• Record Type: Journal Article
• Authors: Mignogna, Carmen; Maddaloni, Ernesto; D'Onofrio, Luca; Buzzetti, Raffaella
• Is Part Of: Expert opinion on investigational drugs. Volume 30:Number 12(2021)
• Page Start: 1209
• Page End: 1219
• Publication Date: 2021-12-02
• Subjects: Anti-CD3 -- high-risk type 1 diabetes -- monoclonal antibodies -- otelixizumab -- prevention -- teplizumab -- type 1 diabetes; Drugs -- Design -- Periodicals; Drugs, Investigational -- Bibliography; Drugs, Investigational -- Periodicals; 615.1
• DOI: 10.1080/13543784.2022.2022119
• Languages: English
• ISSNs: 1354-3784

Abstract

ABSTRACT: Introduction: Immunotherapies for type 1 diabetes mellitus (T1D) have been the focus of intense research over the past few decades. Nevertheless, the results of clinical trials have not matched expectations. However, thanks to the recent and promising results on T1D prevention, among all the different immune-intervention strategies, clinical evidence on anti-CD3 monoclonal antibodies (mAb) deserves particular attention and in-depth evaluation. Areas covered: In this narrative review, we introduce the role of T-cells and their co-receptor CD3 in the pathogenesis of T1D and examine the potential of anti-CD3 mAbs as a treatment for preventing or curing T1D. We discuss pre-clinical studies and phase II/III clinical trials testing the anti-CD3 mAb teplizumab in subjects at T1D high risk, and testing teplizumab and otelixizumab in T1D recent onset patients. In this work, we discuss the current evidence gathered on anti-CD3 therapy to offer insights on the treatment strengths, limitations, and unmet needs. Expert opinion: Recent phase II clinical trials with teplizumab in individuals at high-risk of developing T1D seem encouraging, but benefits associated with the use of anti-CD3 mAb in recent-onset T1D are still controversial. A better patient selection, based on immunological profiles and specific biomarkers, is crucial to improve clinical outcomes in T1D immunotherapies.