Treatment of patients with new onset type 1 diabetes with a single course of anti-CD3 mAb teplizumab preserves insulin production for up to 5 years
Open accessAbstract
Anti-CD3 mAbs may prolong beta cell function up to 2 years in patients with new onset Type 1 diabetes (T1DM). A randomized open label trial of anti-CD3 mAb, Teplizumab, in T1DM was stopped after 10 subjects because of increased adverse events than in a previous trial related with higher dosing of drug. Teplizumab caused transient reduction in circulating T cells, but the recovered cells were not new thymic emigrants because T cell receptor excision circles were not increased. There was a trend for reduced loss of C-peptide over 2 years with drug treatment (p=0.1), and insulin use was lower (p<0.001). In 4 drug-treated subjects followed up to 60 months, C-peptide responses were maintained. We conclude that increased doses of Teplizumab are associated with greater adverse events without improved efficacy. The drug may marginate rather than deplete T cells. C-peptide levels may remain detectable up to 5 years after treatment.
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The drug categories that preserve C-peptide include rituximab, teplizumab, otelixizumab, abatacept, and alefacept.
“These drugs include a monoclonal antibody against the B-cell CD20 receptor (rituximab),147 monoclonal antibodies against the T-cell CD3 receptor (teplizumab148,149 and otelixizumab150), cytotoxic T-lymphocyte protein 4 (CTLA4)-immunoglobulin-mediated co-stimulatory blockade with abatacept,151 and alefacept,152”
From Type 1 diabetes (2018) · cites this paper as [148]
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- Authors
- Herold, K. C., Gitelman, S., Greenbaum, C., Puck, J., Hagopian, W., Gottlieb, P., Sayre, P., Bianchine, P., Wong, E., Seyfert-Margolis, V., Bourcier, K., & Bluestone, J. A.
- Affiliations
- Yale University (US)
- University of California, San Francisco (US)
- Benaroya Research Institute (US)
- University of Washington (US)
- University of Colorado Denver (US)
- Immune Tolerance Network (US)
- National Institutes of Health (US)
- Pharmaceutical Product Development (United States) (US)
- Corresponding author
- Herold, Kevan C.
- ORCID
- Venue
- Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 132
- Issue
- 2
- Pages
- 166-173
- ISSN
- 1521-6616 (ISSN-L)
- PMC
- PMC2735402
- OpenAlex
- W1969468597
- Cited by
- 219
- References
- 23
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 11 · 2023: 9 · 2022: 3 · 2021: 9 · 2020: 7 · 2019: 2 · 2018: 6 · 2017: 6 · 2016: 9 · 2015: 13 · 2014: 18 · 2013: 26 · 2012: 33
- FWCI
- 16.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- US Immunodeficiency Network
- National Institutes of Health (n01ai15416-28-0-11)
- University of California, San Francisco
- National Institute of Allergy and Infectious Diseases (N01-AI-15416-3700)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-057846, R01DK057846)
- National Center for Research Resources (UL1RR024131, M01 RR00069, M01-RR 00037, M01RR000069, M01RR000037, UL1RR024139)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- teplizumab, anti-CD3 monoclonal antibody, type 1 diabetes, recent-onset type 1 diabetes, beta-cell function, C-peptide, insulin requirement, T cell depletion, TREC, adverse events, long-term follow-up
- MeSH terms
- Adolescent, C-Peptide, Child, Diabetes Mellitus, Type 1, Exanthema, Female, Fever, Follow-Up Studies, Gastrointestinal Diseases, Humans, Hypoglycemic Agents, Insulin, Male, Nausea, Vomiting, Muromonab-CD3, Treatment Outcome, CD3 Complex, Antibodies, Monoclonal, Humanized
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