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2000
Volume 21, Issue 1
  • ISSN: 1573-3998
  • E-ISSN: 1875-6417

Abstract

Type 1 diabetes (T1D) is a chronic autoimmune disease caused by CD4+ and CD8+ that are activated CD3+ cells and finally lead to the macrophages destroying the beta cells in the pancreas thereby causing diabetes. The anti-CD3 humanized monoclonal antibody was approved on 17th November 2022 by the United States Food Drug Administration (USFDA) with the name teplizumab and the brand name TZIELD. This is the only approved drug that treats type 1 diabetes (T1D) by delaying the onset of stage 3 in type 1 diabetes (T1D). This review outlines essential features of teplizumab including its brief introduction to its mechanism and other therapies for the treatment and various risks as well as the pharmacokinetics and pharmacodynamics of this disease and the clinical trial reports for the completed and ongoing therapies.

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2024-01-25
2025-06-16
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References

  1. AssociationAD Diagnosis and classification of diabetes mellitus.Diabetes Care201033Suppl 1)(Suppl. 1S62910.2337/dc10‑S062 20042775
    [Google Scholar]
  2. KatsarouA. GudbjörnsdottirS. RawshaniA. Type 1 diabetes mellitus.Nat. Rev. Dis. Primers2017311701610.1038/nrdp.2017.16 28358037
    [Google Scholar]
  3. GillespieK.M. Type 1 diabetes: Pathogenesis and prevention.CMAJ2006175216517010.1503/cmaj.060244 16847277
    [Google Scholar]
  4. RapiniN. SchiaffiniR. FierabracciA. Immunotherapy strategies for the prevention and treatment of distinct stages of type 1 diabetes: An overview.Int. J. Mol. Sci.2020216210310.3390/ijms21062103 32204344
    [Google Scholar]
  5. DevendraD. LiuE. EisenbarthG.S. Type 1 diabetes: Recent developments.BMJ2004328744275075410.1136/bmj.328.7442.750 15044291
    [Google Scholar]
  6. GiwaA.M. AhmedR. OmidianZ. Current understandings of the pathogenesis of type 1 diabetes: Genetics to environment.World J. Diabetes2020111132510.4239/wjd.v11.i1.13 31938470
    [Google Scholar]
  7. BurrackA.L. MartinovT. FifeB.T. T cell-mediated beta cell destruction: Autoimmunity and alloimmunity in the context of type 1 diabetes.Front. Endocrinol. (Lausanne)2017834310.3389/fendo.2017.00343 29259578
    [Google Scholar]
  8. RathodS. Novel Insights into the Immunotherapy-Based Treatment Strategy for Autoimmune Type 1 Diabetes.Diabetology202231799610.3390/diabetology3010007
    [Google Scholar]
  9. von ScholtenB.J. KreinerF.F. GoughS.C.L. von HerrathM. Current and future therapies for type 1 diabetes.Diabetologia20216451037104810.1007/s00125‑021‑05398‑3 33595677
    [Google Scholar]
  10. GitelmanS.E. GottliebP.A. RigbyM.R. Antithymocyte globulin treatment for patients with recent-onset type 1 diabetes: 12-month results of a randomised, placebo-controlled, phase 2 trial.Lancet Diabetes Endocrinol.20131430631610.1016/S2213‑8587(13)70065‑2 24622416
    [Google Scholar]
  11. OrbanT. BundyB. BeckerD.J. Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes: Follow-up 1 year after cessation of treatment.Diabetes Care20143741069107510.2337/dc13‑0604 24296850
    [Google Scholar]
  12. RigbyM.R. HarrisK.M. PinckneyA. Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients.J. Clin. Invest.201512583285329610.1172/JCI81722 26193635
    [Google Scholar]
  13. BenderC. Rodriguez-CalvoT. AmirianN. CoppietersK.T. von HerrathM.G. The healthy exocrine pancreas contains preproinsulin-specific CD8 T-cells that attack islets in type 1 diabetes.Sci. Adv.2020642eabc558610.1126/sciadv.abc5586 33067232
    [Google Scholar]
  14. ForoutanN. HopkinsR.B. TarrideJ.E. FlorezI.D. LevineM. Safety and efficacy of active and passive immunotherapy in mild-to-moderate Alzheimer’s disease: A systematic review and network meta-analysis.Clin. Invest. Med.2019421E53E6510.25011/cim.v42i1.32393 30904037
    [Google Scholar]
  15. CoulieP.G. Van den EyndeB.J. van der BruggenP. BoonT. Tumour antigens recognized by T lymphocytes: At the core of cancer immunotherapy.Nat. Rev. Cancer201414213514610.1038/nrc3670 24457417
    [Google Scholar]
  16. SpeakeC. GreenbaumC.J. Approval of teplizumab: Implications for patients.Nat. Rev. Endocrinol.202319737737810.1038/s41574‑023‑00849‑w 37202589
    [Google Scholar]
  17. HirschJ.S. FDA approves teplizumab: A milestone in type 1 diabetes.Lancet Diabetes Endocrinol.2022 36436528
    [Google Scholar]
  18. ChristensenJ. GoodmanB. FDA approves first treatment to delay onset of type 1 diabetes CNN.2022Available From: https://edition.cnn.com/2022/11/17/health/tzield-teplizumab-diabetic-treatment/index.html
  19. LeonF. Methods and compositions for preventing type 1 diabetes.US11434291B22022
    [Google Scholar]
  20. Provention BioTeplizumab for the delay of progression to clinical stage 3 type 1 diabetes in at-risk patients.2021Available From: https://www.fda.gov/media/149389/download
  21. GagliaJ. KisslerS. Anti-CD3 antibody for the prevention of type 1 diabetes: A story of perseverance.Biochemistry201958404107411110.1021/acs.biochem.9b00707 31523950
    [Google Scholar]
  22. SimsE.K. BundyB.N. StierK. Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals.Sci. Transl. Med.202113583eabc898010.1126/scitranslmed.abc8980 33658358
    [Google Scholar]
  23. Smigoc SchweigerD. Recent advances in immune-based therapies for type 1 diabetes.Horm. Res. Paediatr.202296611510.1159/000524866 35533645
    [Google Scholar]
  24. Provention Bio Teplizumab Prescribing informationTZIELD™ (teplizumab-mzwv) injection, for intravenous use.2022Available From: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761183s000lbl.pdf
  25. HeroldK.C. BundyB.N. LongS.A. An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes.N. Engl. J. Med.2019381760361310.1056/NEJMoa1902226 31180194
    [Google Scholar]
  26. InselR.A. DunneJ.L. AtkinsonM.A. Staging presymptomatic type 1 diabetes: A scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association.Diabetes Care201538101964197410.2337/dc15‑1419 26404926
    [Google Scholar]
  27. GreenbaumC.J. BeamC.A. BoulwareD. Fall in C-peptide during first 2 years from diagnosis: Evidence of at least two distinct phases from composite Type 1 Diabetes TrialNet data.Diabetes20126182066207310.2337/db11‑1538 22688329
    [Google Scholar]
  28. WherrettD.K. ChiangJ.L. DelamaterA.M. Defining pathways for development of disease-modifying therapies in children with type 1 diabetes: A consensus report.Diabetes Care201538101975198510.2337/dc15‑1429 26404927
    [Google Scholar]
  29. HeroldK.C. GitelmanS.E. EhlersM.R. Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: Metabolic and immunologic features at baseline identify a subgroup of responders.Diabetes201362113766377410.2337/db13‑0345 23835333
    [Google Scholar]
  30. SherryN. HagopianW. LudvigssonJ. Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial.Lancet2011378979048749710.1016/S0140‑6736(11)60931‑8 21719095
    [Google Scholar]
  31. AtkinsonM.A. RoepB.O. PosgaiA. WheelerD.C.S. PeakmanM. The challenge of modulating β-cell autoimmunity in type 1 diabetes.Lancet Diabetes Endocrinol.201971526410.1016/S2213‑8587(18)30112‑8 30528099
    [Google Scholar]
  32. HeroldK.C. VignaliD.A.A. CookeA. BluestoneJ.A. Type 1 diabetes: Translating mechanistic observations into effective clinical outcomes.Nat. Rev. Immunol.201313424325610.1038/nri3422 23524461
    [Google Scholar]
  33. NoureldenA.Z. ElshanbaryA.A. El-SherifL. Safety and efficacy of teplizumab for treatment of type one diabetes mellitus: A systematic review and meta-analysis.Endocr. Metab. Immune Disord. Drug Targets202121101895190410.2174/1871530320999201209222921 33302842
    [Google Scholar]
  34. ZhengP. LiZ. ZhouZ. Gut microbiome in type 1 diabetes: A comprehensive review.Diabetes Metab. Res. Rev.2018347e304310.1002/dmrr.3043 29929213
    [Google Scholar]
  35. Waldron-LynchF. HenegariuO. DengS. Preston-HurlburtP. TooleyJ. FlavellR. Teplizumab induces human gut-tropic regulatory cells in humanized mice and patients.Sci. Transl. Med.20124118118ra1210.1126/scitranslmed.3003401
    [Google Scholar]
  36. YuH. GaglianiN. IshigameH. Intestinal type 1 regulatory T-cells migrate to periphery to suppress diabetogenic T-cells and prevent diabetes development.Proc. Natl. Acad. Sci. USA201711439104431044810.1073/pnas.1705599114 28894001
    [Google Scholar]
  37. WoodleE.S. XuD. ZivinR.A. Phase I trial of a humanized, fc receptor nonbinding okt3 antibody, huOKT3??1 (Ala-Ala) in the treatment of acute renal allograft rejection.Transplantation199968560861610.1097/00007890‑199909150‑00003 10507477
    [Google Scholar]
  38. HeringJ. Insulin independence after single-donor islet transplantation in type 1 diabetes with hOKT3γ-1 (ala-ala), sirolimus, and tacrolimus therapy.Am. J. Transplant.20011180
    [Google Scholar]
  39. HeringB.J. KandaswamyR. HarmonJ.V. Transplantation of cultured islets from two-layer preserved pancreases in type 1 diabetes with anti-CD3 antibody.Am. J. Transplant.20044339040110.1046/j.1600‑6143.2003.00351.x 14961992
    [Google Scholar]
  40. SkylerJ.S. GreenbaumC.J. LachinJ.M. Type 1 Diabetes TrialNet--an international collaborative clinical trials network.Ann. N. Y. Acad. Sci.200811501142410.1196/annals.1447.054 19120262
    [Google Scholar]
  41. UtsetT.O. AugerJ.A. PeaceD. Modified anti-CD3 therapy in psoriatic arthritis: A phase I/II clinical trial.J. Rheumatol.200229919071913 12233885
    [Google Scholar]
  42. PerdigotoA.L. Preston-HurlburtP. ClarkP. Treatment of type 1 diabetes with teplizumab: Clinical and immunological follow-up after 7 years from diagnosis.Diabetologia201962465566410.1007/s00125‑018‑4786‑9 30569273
    [Google Scholar]
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