Combination immunotherapy for type 1 diabetes
Open accessAbstract
Purpose of review Type 1 diabetes (T1D) is an autoimmune disease marked by β-cell destruction. Immunotherapies for T1D have been investigated since the 1980s and have focused on restoration of tolerance, T cell or B cell inhibition, regulatory T cell (Treg) induction, suppression of innate immunity and inflammation, immune system reset, and islet transplantation. The purpose of this review is to provide an overview and lessons learned from single immunotherapy trials, describe recent and ongoing combination immunotherapy trials, and provide perspectives on strategies for future combination clinical interventions aimed at preserving insulin secretion in T1D.Recent findings Combination immunotherapies have had mixed results in improving short-term glycemic control and insulin secretion in recent-onset T1D. A handful of studies have successfully reached their primary end-point of improved insulin secretion in recent-onset T1D. However, long-term improvements glycemic control and the restoration of insulin independence remain elusive. Future interventions should focus on strategies that combine immunomodulation with efforts to alleviate β-cell stress and address the formation of antigens that activate autoimmunity.
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Ongoing trials are testing agents that worked against β-cell stress in mouse diabetes models.
“several ongoing trials are testing drugs that have successfully targeted β-cell stress responses in mouse models of diabetes.170”
From Type 1 diabetes (2018) · cites this paper as [170]
The Single immunotherapies section reports that imatinib protected β cells in mouse models and was being tested in a phase II trial. The Concluding Remarks report that imatinib suppresses β-cell ER stress and that a trial of the ER-stress–alleviating drug TUDCA was underway. The paper does not establish that several drugs in ongoing trials had each successfully targeted β-cell stress responses in mouse diabetes models. (LLM, conf=0.85)
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References 124 · Cited by 41
- Authors
- Bone, R. N., & Evans-Molina, C.
- Affiliations
- Indiana University Indianapolis (US)
- ORCID
- Bone, Robert N.
- Venue
- Current Diabetes Reports
- Published
- 2017-05-22
- Volume
- 17
- Issue
- 7
- Pages
- 50-50
- ISSN
- 1534-4827 (ISSN-L)
- 1539-0829
- PMC
- PMC5774222
- OpenAlex
- W2619948084
- Cited by
- 41
- References
- 124
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 4 · 2021: 6 · 2020: 2 · 2019: 3 · 2018: 5
- FWCI
- 0.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Diabetes Reports (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Author eBooks
- Funders
- U.S. Department of Veterans Affairs (I01-BX001733, I01 BX000733)
- National Institute of Allergy and Infectious Diseases (T32AI060519)
- National Institute of Diabetes and Digestive and Kidney Diseases (UC4DK104166, R01DK093954)
- 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
- type 1 diabetes, combination immunotherapy, beta cell destruction, immune tolerance, regulatory T cells, T cell suppression, B cell inhibition, islet transplantation, insulin secretion, glycemic control, recent-onset type 1 diabetes, beta-cell stress, clinical trials
- MeSH terms
- Insulin Secretion, Animals, Clinical Trials as Topic, Diabetes Mellitus, Type 1, Humans, Immunity, Innate, Immunotherapy, Insulin
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