Investigational therapies targeting CD3 for prevention and treatment of type 1 diabetes

References

• Patterson C, Gyürüs E, Rosenbauer J, et al. Seasonal variation in month of diagnosis in children with type 1 diabetes registered in 23 European centers during 1989-2008: little short-term influence of sunshine hours or average temperature. Pediatr Diabetes. 2015;16:573–580.
   PubMed Web of Science ®Google Scholar
• Renard E, Ikegami H, Daher Vianna AG, et al. The SAGE study: global observational analysis of glycaemic control, hypoglycaemia and diabetes management in T1DM. Diabetes Metab Res Rev. 2021;37(7). DOI:https://doi.org/10.1002/dmrr.3430
   Google Scholar
• Sims EK, Bundy BN, Stier K, et al. Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals. Sci Transl Med. 2021;13:eabc8980.
   PubMed Web of Science ®Google Scholar
• Cohen J. Statistical power: analysis for the behavioural sciences. New York:: Academic Press; 1977.
   Google Scholar
• Willcox A, Richardson SJ, Bone AJ, et al. Analysis of islet inflammation in human type 1 diabetes. Clin Exp Immunol. 2009;155:173–181.
   PubMed Web of Science ®Google Scholar
• Dong D, Zheng L, Lin J, et al. Structural basis of assembly of the human T cell receptor–CD3 complex. Nature. 2019;573:546–552.
   PubMed Web of Science ®Google Scholar
• Fischer A, de Saint Basile G, Le Deist F. CD3 deficiencies. Curr Opin Allergy Clin Immunol. 2005;5:491–495.
   PubMed Web of Science ®Google Scholar
• Dadi HK, Simon AJ, Roifman CM. Effect of CD3delta deficiency on maturation of alpha/beta and gamma/delta T-cell lineages in severe combined immunodeficiency. N Engl J Med. 2003;349:1821–1828.
   PubMed Web of Science ®Google Scholar
• Chatenoud L, Baudrihaye MF, Kreis H, et al. Human in vivo antigenic modulation induced by the anti-T cell OKT3 monoclonal antibody. Eur J Immunol. 1982;12:979–982.
   PubMed Web of Science ®Google Scholar
• Kuhn C, Weiner HL. Therapeutic anti-CD3 monoclonal antibodies: from bench to bedside. Immunotherapy. 2016;8:889–906.
   PubMed Web of Science ®Google Scholar
• Penaranda C, Tang Q, Bluestone JA. Anti-CD3 therapy promotes tolerance by selectively depleting pathogenic cells while preserving regulatory T cells. J Immunol. 2011;187:2015–2022.
   PubMed Web of Science ®Google Scholar
• Roep BO, Thomaidou S, van Tienhoven R, et al. Type 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system?). Nat Rev Endocrinol. 2021;17:150–161.
   PubMed Web of Science ®Google Scholar
• Pozzilli P, Maddaloni E, Buzzetti R. Combination immunotherapies for type 1 diabetes mellitus. Nat Rev Endocrinol. 2015;11:289–297.
   PubMed Web of Science ®Google Scholar
• Reinherz EL, Hussey RE, Schlossman SF. A monoclonal antibody blocking human T cell function. Eur J Immunol. 1980;10:758–762.
   PubMed Web of Science ®Google Scholar
• Chatenoud L, Ferran C, Reuter A, et al. Systemic reaction to the anti-T-cell monoclonal antibody OKT3 in relation to serum levels of tumor necrosis factor and interferon-gamma [corrected]. N Engl J Med. 1989;320:1420–1421.
   PubMed Web of Science ®Google Scholar
• Ferran C, Sheehan K, Dy M, et al. Cytokine-related syndrome following injection of anti-CD3 monoclonal antibody: further evidence for transient in vivo T cell activation. Eur J Immunol. 1990;20:509–515.
   PubMed Web of Science ®Google Scholar
• Gaglia J, Kissler S. Anti-CD3 antibody for the prevention of type 1 diabetes: a story of perseverance. Biochemistry. 2019;58:4107–4111.
   PubMed Web of Science ®Google Scholar
• Vossen AC, Tibbe GJ, Kroos MJ, et al. Fc receptor binding of anti-CD3 monoclonal antibodies is not essential for immunosuppression, but triggers cytokine-related side effects. Eur J Immunol. 1995;25:1492–1496.
   PubMed Web of Science ®Google Scholar
• Alegre ML, Peterson LJ, Xu D, et al. A non-activating “humanized” anti-CD3 monoclonal antibody retains immunosuppressive properties in vivo. Transplantation. 1994;57:1537–1543.
   PubMed Web of Science ®Google Scholar
• Bolt S, Routledge E, Lloyd I, et al. The generation of a humanized, non-mitogenic CD3 monoclonal antibody which retains in vitro immunosuppressive properties. Eur J Immunol. 1993;23:403–411.
   PubMed Web of Science ®Google Scholar
• Hayward AR, Shreiber M. Neonatal injection of CD3 antibody into nonobese diabetic mice reduces the incidence of insulitis and diabetes. J Immunol. 1989;143:1555–1559.
   PubMed Web of Science ®Google Scholar
• Chatenoud L, Thervet E, Primo J, et al. Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. Proc Natl Acad Sci U S A. 1994;91:123–127.
   PubMed Web of Science ®Google Scholar
• Chatenoud L, Primo J, Bach JF. CD3 antibody-induced dominant self tolerance in overtly diabetic NOD mice. J Immunol. 1997;158:2947–2954.
   PubMed Web of Science ®Google Scholar
• Herold KC, Bluestone JA, Montag AG, et al. Prevention of autoimmune diabetes with nonactivating anti-CD3 monoclonal antibody. Diabetes. 1992;41:385–391.
   PubMed Web of Science ®Google Scholar
• Ishikawa H, Ochi H, Chen M-L, et al. Inhibition of autoimmune diabetes by oral administration of anti-CD3 monoclonal antibody. Diabetes. 2007;56:2103–2109.
   PubMed Web of Science ®Google Scholar
• Xin GLL, Khee YP, Ying TY, et al. Current status on immunological therapies for type 1 diabetes mellitus. Curr Diab Rep. 2019;19(5). DOI:https://doi.org/10.1007/s11892-019-1144-3
   Google Scholar
• Herold KC, Hagopian W, Auger JA, et al. Anti-CD3 monoclonal antibody in new-onset Type 1 Diabetes Mellitus. N Engl J Med. 2002;346(22):1692–1698.
   PubMed Web of Science ®Google Scholar
• Herold KC, Gitelman SE, Masharani U, et al. A single course of Anti-CD3 monoclonal antibody responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes. 2005;54(6):1763–1769.
   PubMed Web of Science ®Google Scholar
• Keymeulen B, Vandemeulebroucke E, Ziegler AG, et al. Insulin needs after CD3-Antibody therapy in new-onset type 1 diabetes. N Engl J Med.. 2005;352(25):2598–2608.
   PubMed Web of Science ®Google Scholar
• Herold KC, Gitelman S, Greenbaum C, et al. 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. Clin Immunol. 2009;132:166–173.
   PubMed Web of Science ®Google Scholar
• Keymeulen B, Walter M, Mathieu C, et al. Four-year metabolic outcome of a randomised controlled CD3-antibody trial in recent-onset type 1 diabetic patients depends on their age and baseline residual beta cell mass. Diabetologia. 2010;53(4):614–623.
   PubMed Web of Science ®Google Scholar
• Sherry N, Hagopian W, Ludvigsson J, et al. Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial. Lancet. 2011;60931–60938. DOI:https://doi.org/10.1016/S0140-6736(11)60931-8.
   Google Scholar
• Hagopian W, Ferry RJ, Sherry N, et al. Teplizumab preserves C-peptide in recent-onset type 1 diabetes: two-year results from the randomized, placebo-controlled Protégé trial. Diabetes. 2013;62(11):3901–3908.
   PubMed Web of Science ®Google Scholar
• Herold KC, Gitelman SE, Ehlers MR, et al. 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. Diabetes. 2013;62(11):3766–3774.
   PubMed Web of Science ®Google Scholar
• Aronson R, Gottlieb PA, Christiansen JS, et al. Low-dose otelixizumab anti-CD3 monoclonal antibody DEFEND-1 study: results of the randomized phase III study in recent-onset human type 1 diabetes. Diabetes Care. 2014;37(10):2746–2754.
   PubMed Web of Science ®Google Scholar
• Ambery P, Donner TW, Biswas N, et al. Efficacy and safety of low-dose otelixizumab anti-CD3 monoclonal antibody in preserving C-peptide secretion in adolescent type 1 diabetes: DEFEND-2, a randomized, placebo-controlled, double-blind, multi-centre study. Diabet Med. 2014;31(4):399–402.
   PubMed Web of Science ®Google Scholar
• Long SA, Thorpe J, Herold KC, et al. Remodeling T cell compartments during anti-CD3 immunotherapy of type 1 diabetes. Cell Immunol. 2017;319:3–9.
   PubMed Web of Science ®Google Scholar
• Perdigoto AL, Preston-Hurlburt P, Clarke P, et al. Treatment of type 1 diabetes with teplizumab: clinical and immunological follow-up after 7 years from diagnosis. Diabetologia. 2019;62(4):655–664.
   PubMed Web of Science ®Google Scholar
• Herold KC, Bundy BN, Long SA, et al. An Anti-CD3 antibody, Teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med. 219;381(7):603–613.
   Google Scholar
• Keymeulen B, van Maurik A, Inman D, et al. A randomised, single-blind, placebo-controlled, dose-finding safety and tolerability study of the anti-CD3 monoclonal antibody otelixizumab in new-onset type 1 diabetes. Diabetologia. 2021;64(2):313–324.
   PubMed Web of Science ®Google Scholar
• Steele C, Hagopian WA, Gitelman S, et al. Insulin secretion in type 1 diabetes. Diabetes. 2004;53(2):426–433.
   PubMed Web of Science ®Google Scholar
• Sherry NA, Kushner JA, Glandt M, et al. Effects of autoimmunity and immune therapy on beta-cell turnover in type 1 diabetes. Diabetes. 2006;55:3238–3245.
   PubMed Web of Science ®Google Scholar
• Atkinson MA, Roep BO, Posgai A, et al. The challenge of modulating β-cell autoimmunity in type 1 diabetes. Lancet Diabetes Endocrinol. 2019;30112–30118. DOI:https://doi.org/10.1016/S2213-8587(18).
   Google Scholar
• Antonelli A, Fallahi P, Ferrari SM, et al. Serum Th1 (CXCL10) and Th2 (CCL2) chemokine levels in children with newly diagnosed Type 1 diabetes: a longitudinal study. Diabet Med. 2008; DOI:https://doi.org/10.1111/j.1464-5491.2008.02577.x.
   Google Scholar
• Keir ME, Francisco LM, Sharpe AH. PD-1 and its ligands in T-cell immunity. Curr Opin Immunol. 2007;19(3):309–314.
   PubMed Web of Science ®Google Scholar
• Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–1034.
   PubMed Web of Science ®Google Scholar
• Keymeulen B, Candon s, Fafi-Kremer S, et al. Transient Epstein-Barr virus reactivation in CD3 monoclonal antibody-treated patients. Blood. 2010;115(6):1145–1155.
   PubMed Web of Science ®Google Scholar
• Buzzetti R, Zampetti S, Maddaloni E. Adult-onset autoimmune diabetes: current knowledge and implications for management. Nat Rev Endocrinol. 2017;13:674–686.
   PubMed Web of Science ®Google Scholar
• Silvia P, Simona Z, Ernesto M, et al. “H” for heterogeneity in the algorithm for type 2 diabetes management. Curr Diab Rep. 2020;20(5). DOI:https://doi.org/10.1007/s11892-020-01297-w
   Google Scholar
• de Brito MF, Torre C, Silva-Lima B. Scientific advances in diabetes: the impact of the innovative medicines initiative. Front Med. 2021;8. DOI:https://doi.org/10.3389/fmed.2021.688438
   Google Scholar
• Chatenoud L, Legendre C, Ferran C, et al. Corticosteroid inhibition of the OKT3 — induced cytokine-related syndrome-dosage and kinetics prerequisites. Transplantation. 1991;51(2):334–337.
   PubMed Web of Science ®Google Scholar
• Ferran C, Dy M, Merite S, et al. Reduction of morbidity and cytokine release in anti-CD3 Moab-treated mice by corticosteroids. Transplantation. 1990;50(4):642–648.
   PubMed Web of Science ®Google Scholar
• Charpentier B, Hiesse C, Lantz O, et al. Evidence that antihuman tumor necrosis factor monoclonal antibody prevents OKT3-induced acute syndrome. Transplantation. 1992;54(6):997–1001.
   PubMed Web of Science ®Google Scholar
• Ochi H, Abraham M, Ishikawa H, et al. New immunosuppressive approaches: oral administration of CD3-specific antibody to treat autoimmunity. J Neurol Sci. 2008;274(1–2):9–12.
   PubMed Web of Science ®Google Scholar
• Ilan Y, Zigmond E, Lalazar G, et al. Oral administration of OKT3 monoclonal antibody to human subjects induces a dose-dependent immunologic effect in T cells and dendritic cells. J Clin Immunol. 2010;30(1):167–177.
   PubMed Web of Science ®Google Scholar
• Lalazar G, Mizrahi M, Turgeman I, et al. Oral administration of OKT3 mab to patients with NASH, promotes regulatory t-cell induction, and alleviates insulin resistance: results of a phase iia blinded placebo-controlled trial. J Clin Immunol. 2015;35(4):399–407.
   PubMed Web of Science ®Google Scholar
• Lapolla A, Berra C, Boemi M, et al. Long-Term effectiveness of liraglutide for treatment of type 2 diabetes in a real-life setting: a 24-month, multicenter, non-interventional, retrospective study. Adv Ther. 2018;35(2):243–253.
   PubMed Web of Science ®Google Scholar
• D’Onofrio L, Mignogna C, Carlone A, et al. Decrease of coronary heart disease risk with GLP1-receptor agonists or SGLT2 inhibitors therapy in patients with type 2 diabetes in primary cardiovascular prevention: a 24 months follow-up study. Diabetes Res Clin Pract. 2021;173: DOI:https://doi.org/10.1016/j.diabres.2021.108681.
   Google Scholar
• Sherry NA, Chen W, Kushner JA, et al. Exendin-4 improves reversal of diabetes in NOD mice treated with anti-CD3 monoclonal antibody by enhancing recovery of beta-cells. Endocrinology. 2007;148(11):5136–5144.
   PubMed Web of Science ®Google Scholar
• Pozzilli P, Bosi E, Cirkel D, et al. (2020). Randomized 52-week Phase 2 Trial of Albiglutide Versus Placebo in Adult Patients With Newly Diagnosed Type 1 Diabetes. The Journal of Clinical Endocrinology & Metabolism, 105(6), e2192–e2206. https://doi.org/10.1210/clinem/dgaa149
   Web of Science ®Google Scholar