The Cross-Clade Neutralizing Activity of a Human Monoclonal Antibody Is Determined by the GPGR V3 Motif of HIV Type 1

With the introduction of immune checkpoint inhibitors into clinical practice, various autoimmune toxicities have been described. Antibodies targeting the receptor:ligand pairing of programmed death receptor-1 (PD-1) and its cognate ligand programmed death-ligand 1 (PD-L1) in rare reports have been associated with autoimmune diabetes mellitus. We report 2 cases of rapid-onset, insulin-dependent, type 1 diabetes mellitus in the setting of administration of nivolumab, a fully human monoclonal antibody to PD-1, and atezolizumab, a humanized monoclonal antibody to PD-L1. This appears to be the first report of autoimmune diabetes mellitus associated with atezolizumab. In addition, we provide a brief review of similar cases reported in the literature and a discussion of potential mechanisms for this phenomenon and propose a diagnostic and treatment algorithm.

Download Full-text

Teplizumab for Treatment of Type 1 Diabetes Mellitus

Annals of Pharmacotherapy ◽

10.1345/aph.1r065 ◽

2012 ◽

Vol 46 (10) ◽

pp. 1405-1412 ◽

Cited By ~ 3

Author(s):

Jessica W Skelley ◽

Lindsey K Elmore ◽

Jeffrey A Kyle

Keyword(s):

Diabetes Mellitus ◽

Monoclonal Antibody ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Human Monoclonal Antibody ◽

Clinical Trial Data ◽

Data Sources ◽

Β Cells ◽

Phase 3

Objective: To review the pharmacology, pharmacokinetics, safety, and efficacy of teplizumab and evaluate relevant clinical trial data. Data Sources: Searches of MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, American Diabetes Association scientific posters, and Google Scholar (1966-May 2012) were conducted using the key words teplizumab. anti-CD3 monoclonal antibody, MGA031, and hOKT3γ1 (Ala-Ala). Searches were limited to articles published in English. Study Selection and Data Extraction: Clinical trials evaluating teplizumab for type 1 diabetes mellitus (T1DM) published in English were selected from the data sources. All published relevant abstracts were included. References cited in identified articles were used for additional citations. Data Synthesis: T1DM accounts for up to 10% of all cases of diabetes mellitus, T1DM is characterized as a chronic and progressive autoimmune disease leading to the destruction of insulin-producing β-cells of the pancreas. Teplizumab is a humanized Fc-mutated anti-CD3 monoclonal antibody that alters the function of the T-lymphocytes that mediate the destruction of the insulin-producing β-cells. While clinical data are limited, both Phase 2 and Phase 3 studies have demonstrated preserved C-peptide response as a measure of insulin production, decreased exogenous insulin use, and improved grycemic control following a 12- to 14-day teplizumab infusion in patients diagnosed with T1DM within the previous 6 weeks. However, 1 Phase 3 trial tailed to find the same benefits in those diagnosed with T1DM within the previous 12 weeks when a lower cumulative teplizumab dose was used. Initial studies indicated that teplizumab is well tolerated, with a self-limiting rash as the most commonly reported adverse effect. Conclusions: Teplizumab is an anti-CD3 human monoclonal antibody with promising activity in treatment of patients with T1DM, Results from Phase 3 trials are needed to further determine safety, efficacy, and dosing frequency.

Download Full-text