ArticleScience translational medicine2011
Human CD3 transgenic mice: preclinical testing of antibodies promoting immune tolerance.
Article in Science translational medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- Target engagement and cellular fate of otelixizumab: a repeat dose escalation study of an anti-CD3ε mAb in new-onset type 1 diabetes mellitus patients.British journal of clinical pharmacology · 2019Trial
- Therapeutic Antibodies in Medicine.Molecules (Basel, Switzerland) · 2023Review
- New therapeutic approaches for type 1 diabetes: Disease-modifying therapies.World journal of diabetes · 2022Review
- 100 years post-insulin: immunotherapy as the next frontier in type 1 diabetes.Immunotherapy advances · 2021Review
- A humanized CD3ε-knock-in mouse model for pre-clinical testing of anti-human CD3 therapy.PloS one · 2021Article
- Immunomodulation Followed by Antigen-Specific TDiabetes · 2020Article
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- Article
- Mucosal administration of CD3-specific monoclonal antibody inhibits diabetes in NOD mice and in a preclinical mouse model transgenic for the CD3 epsilon chain.Journal of autoimmunity · 2017Article
- Thinking bedside at the bench: the NOD mouse model of T1DM.Nature reviews. Endocrinology · 2015Review
- Inducing and Administering Tregs to Treat Human Disease.Frontiers in immunology · 2015Review
- Humanized mice as a model for aberrant responses in human T cell immunotherapy.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Article
- Systemic administration of a bispecific antibody targeting EGFRvIII successfully treats intracerebral glioma.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Administration of anti-CD3 antibodies modulates the immune response to an infusion of α-glucosidase in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Clinical immunologic interventions for the treatment of type 1 diabetes.Cold Spring Harbor perspectives in medicine · 2012Review
- Preexisting autoantibodies predict efficacy of oral insulin to cure autoimmune diabetes in combination with anti-CD3.Diabetes · 2012Article
- CD3 monoclonal antibodies: a first step towards operational immune tolerance in the clinic.The review of diabetic studies : RDS · 2012Review
- Induction of immunological tolerance by oral anti-CD3.Clinical & developmental immunology · 2012Review
- Immunomodulatory therapy to preserve pancreatic β-cell function in type 1 diabetes.Nature reviews. Drug discovery · 2011Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Monoclonal antibodies have proven to be potent agents to promote immunological tolerance in animal models of autoimmune disease and transplantation. However, optimal clinical application and pharmaceutical development have been limited by the species specificity of therapeutic antibodies, as well exemplified in the case of anti-CD3 antibodies. Compelling evidence in the nonobese diabetic (NOD) mouse, recently translated to clinical autoimmune insulin-dependent diabetes, demonstrates that a short CD3 antibody treatment effectively and durably controls disease progression. We established transgenic mice expressing the human ε chain of the CD3 complex bred onto the NOD background. These mice developed a high incidence of spontaneous autoimmune diabetes and harbored T cells sensitive both in vitro and in vivo to anti-human CD3 antibodies. Treatment of diabetic transgenic mice with otelixizumab, an anti-human CD3 antibody that has proven effective in the clinic, resulted in durable disease remission dependent on transferable T cell-mediated tolerance. This model should enable the evaluation of anti-human CD3 antibodies to determine their potential clinical utility.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.