Generic placeholder image

Current Diabetes Reviews

Editor-in-Chief

ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

Review Article

Review on Monoclonal Antibodies (mAbs) as a Therapeutic Approach for Type 1 Diabetes

Author(s): Gaurav Agarwal* and Mayank Patel

Volume 20, Issue 7, 2024

Published on: 11 September, 2023

Article ID: e310823220578 Pages: 6

DOI: 10.2174/1573399820666230831153249

Price: $65

Abstract

Monoclonal antibodies have been successfully utilized in a variety of animal models to treat auto-immune illnesses for a long time. Immune system responses will either be less active or more active depending on how the immune system is operating abnormally. Immune system hypoactivity reduces the body's capacity to fight off various invading pathogens, whereas immune system hyperactivity causes the body to attack and kill its own tissues and cells. For maximal patient compliance, we will concentrate on a variety of antibody therapies in this study to treat Type 1 diabetes (an autoimmune condition). T-cells are responsible for the auto-immune condition known as T1D, which causes irregularities in the function of β-cells in the pancreas. As a result, for the treatment and prevention of T1D, immunotherapies that selectively restore continuous beta cellspecific self-tolerance are needed. Utilizing monoclonal antibodies is one way to specifically target immune cell populations responsible for the auto-immune-driven disease (mAb). Numerous mAbs have demonstrated clinical safety and varied degrees of success in modulating autoimmunity, including T1D. A targeted cell population is exhausted by mAb treatments, regardless of antigenic specificity. One drawback of this treatment is the loss of obtained protective immunity. Immune effector cell function is regulated by nondepleting monoclonal antibodies (mAb). The antigenfocused new drug delivery system is made possible by the adaptability of mAbs. For the treatment of T1D and T-cell-mediated autoimmunity, different existing and potential mAb therapy methods are described in this article.

[1]
Katsarou A, Gudbjörnsdottir S, Rawshani A, et al. Type 1 diabetes mellitus. Nat Rev Dis Primers 2017; 3(1): 17016.
[http://dx.doi.org/10.1038/nrdp.2017.16] [PMID: 28358037]
[2]
Quan J, Li TK, Pang H, et al. Diabetes incidence and prevalence in Hong Kong, China during 2006-2014. Diabet Med 2017; 34(7): 902-8.
[http://dx.doi.org/10.1111/dme.13284] [PMID: 27859570]
[3]
Hu D, Hu S, Wan W, et al. Effective optimization of antibody affinity by phage display integrated with high-throughput DNA synthesis and sequencing technologies. PLoS One 2015; 10(6): e0129125.
[http://dx.doi.org/10.1371/journal.pone.0129125] [PMID: 26046845]
[4]
Queen C, Schneider WP, Selick HE, et al. A humanized antibody that binds to the interleukin 2 receptor. Proc Natl Acad Sci 1989; 86(24): 10029-33.
[http://dx.doi.org/10.1073/pnas.86.24.10029] [PMID: 2513570]
[5]
Harding FA, Stickler MM, Razo J, DuBridge R. The immunogenicity of humanized and fully human antibodies. MAbs 2010; 2(3): 256-65.
[http://dx.doi.org/10.4161/mabs.2.3.11641] [PMID: 20400861]
[6]
Edner NM, Heuts F, Thomas N, et al. Follicular helper T-cell profiles predict response to costimulation blockade in type 1 diabetes. Nat Immunol 2020; 21(10): 1244-55.
[http://dx.doi.org/10.1038/s41590-020-0744-z] [PMID: 32747817]
[7]
Keymeulen B, Candon S, Fafi-Kremer S, et al. Transient Epstein-Barr virus reactivation in CD3 monoclonal antibody-treated patients. Blood 2010; 115(6): 1145-55.
[http://dx.doi.org/10.1182/blood-2009-02-204875] [PMID: 20007541]
[8]
Vlasakakis G, Napolitano A, Barnard R, et al. Target engagement and cellular fate of otelixizumab: A repeat dose escalation study of an anti-CD3 mAb in new-onset type 1 diabetes mellitus patients. Br J Clin Pharmacol 2019; 85(4): 704-14.
[http://dx.doi.org/10.1111/bcp.13842] [PMID: 30566758]
[9]
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): 313-24.
[http://dx.doi.org/10.1007/s00125-020-05317-y] [PMID: 33145642]
[10]
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 2019; 381(7): 603-13.
[http://dx.doi.org/10.1056/NEJMoa1902226] [PMID: 31180194]
[11]
Arif S, Tree TI, Astill TP, et al. Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health. J Clin Invest 2004; 113(3): 451-63.
[http://dx.doi.org/10.1172/JCI19585] [PMID: 14755342]
[12]
Gu J, Cheng Y, Wu H, et al. Metallothionein is downstream of Nrf2 and partially mediates sulforaphane prevention of diabetic cardiomyopathy. Diabetes 2017; 66(2): 529-42.
[http://dx.doi.org/10.2337/db15-1274] [PMID: 27903744]
[13]
Pescovitz MD, Greenbaum CJ, Bundy B, et al. B-lymphocyte depletion with rituximab and β-cell function: Two-year results. Diabetes Care 2014; 37(2): 453-9.
[http://dx.doi.org/10.2337/dc13-0626] [PMID: 24026563]
[14]
Chamberlain N, Massad C, Oe T, Cantaert T, Herold KC, Meffre E. Rituximab does not reset defective early B-cell tolerance checkpoints. J Clin Invest 2015; 126(1): 282-7.
[http://dx.doi.org/10.1172/JCI83840] [PMID: 26642366]
[15]
Brezski RJ, Georgiou G. Immunoglobulin isotype knowledge and application to Fc engineering. Curr Opin Immunol 2016; 40: 62-9.
[http://dx.doi.org/10.1016/j.coi.2016.03.002] [PMID: 27003675]
[16]
Sha S, Agarabi C, Brorson K, Lee DY, Yoon S. N-glycosylation design and control of therapeutic monoclonal antibodies. Trends Biotechnol 2016; 34(10): 835-46.
[http://dx.doi.org/10.1016/j.tibtech.2016.02.013] [PMID: 27016033]
[17]
Spolski R, Li P, Leonard WJ. Biology and regulation of IL-2: From molecular mechanisms to human therapy. Nat Rev Immunol 2018; 18(10): 648-59.
[http://dx.doi.org/10.1038/s41577-018-0046-y] [PMID: 30089912]
[18]
Izquierdo C, Ortiz AZ, Presa M, et al. Treatment of T1D via optimized expansion of antigen-specific Tregs induced by IL-2/anti-IL-2 monoclonal antibody complexes and peptide/MHC tetramers. Sci Rep 2018; 8(1): 8106.
[http://dx.doi.org/10.1038/s41598-018-26161-6] [PMID: 29802270]
[19]
Heath EM, Chan SM, Minden MD, Murphy T, Shlush LI, Schimmer AD. Biological and clinical consequences of NPM1 mutations in AML. Leukemia 2017; 31(4): 798-807.
[http://dx.doi.org/10.1038/leu.2017.30] [PMID: 28111462]
[20]
Bhattacharya P, Fan J, Haddad C, et al. A novel pancreatic β-cell targeting bispecific-antibody (BsAb) can prevent the development of Type 1 diabetes in NOD mice. Clin Immunol 2014; 153(1): 187-98.
[http://dx.doi.org/10.1016/j.clim.2014.04.014] [PMID: 24792135]
[21]
Peyrin-Biroulet L, Demarest S, Nirula A. Bispecific antibodies: The next generation of targeted inflammatory bowel disease therapies. Autoimmun Rev 2019; 18(2): 123-8.
[http://dx.doi.org/10.1016/j.autrev.2018.07.014] [PMID: 30572136]
[22]
Gall JM, Davol PA, Grabert RC, Deaver M, Lum LG. T-cells armed with anti-CD3 × anti-CD20 bispecific antibody enhance killing of CD20+ malignant B-cells and bypass complement-mediated rituximab resistance in vitro. Exp Hematol 2005; 33(4): 452-9.
[http://dx.doi.org/10.1016/j.exphem.2005.01.007] [PMID: 15781336]
[23]
Lu CY, Chen GJ, Tai PH, et al. Tetravalent anti-CD20/CD3 bispecific antibody for the treatment of B-cell lymphoma. Biochem Biophys Res Commun 2016; 473(4): 808-13.
[http://dx.doi.org/10.1016/j.bbrc.2016.03.124] [PMID: 27040766]
[24]
Lo Preiato V, Salvagni S, Ricci C, Ardizzoni A, Pagotto U, Pelusi C. Diabetes mellitus induced by immune checkpoint inhibitors: Type 1 diabetes variant or new clinical entity? Review of the literature. Rev Endocr Metab Disord 2021; 22(2): 337-49.
[http://dx.doi.org/10.1007/s11154-020-09618-w] [PMID: 33409866]
[25]
Ke Q, Kroger CJ, Clark M, Tisch RM. Evolving antibody therapies for the treatment of type 1 diabetes. Front Immunol 2021; 11: 624568.
[http://dx.doi.org/10.3389/fimmu.2020.624568] [PMID: 33679717]
[26]
Alghamdi M, Alasmari D, Assiri A, et al. An overview of the intrinsic role of citrullination in autoimmune disorders. J Immunol Res 2019; 2019: 1-39.
[http://dx.doi.org/10.1155/2019/7592851] [PMID: 31886309]
[27]
Martin A, Tisch RM, Getts DR. Manipulating T cell-mediated pathology: Targets and functions of monoclonal antibody immunotherapy. Clin Immunol 2013; 148(1): 136-47.
[http://dx.doi.org/10.1016/j.clim.2013.04.011] [PMID: 23688653]
[28]
Knight DM, Wagner C, Jordan R, et al. The immunogenicity of the 7E3 murine monoclonal Fab antibody fragment variable region is dramatically reduced in humans by substitution of human for murine constant regions. Mol Immunol 1995; 32(16): 1271-81.
[http://dx.doi.org/10.1016/0161-5890(95)00085-2] [PMID: 8559151]
[29]
Fu Y, Lin Q, Zhang Z, Zhang L. Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity. Acta Pharm Sin B 2020; 10(3): 414-33.
[http://dx.doi.org/10.1016/j.apsb.2019.08.010] [PMID: 32140389]
[30]
Hu C, Rodriguez-Pinto D, Du W, et al. Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice. J Clin Invest 2007; 117(12): 3857-67.
[http://dx.doi.org/10.1172/JCI32405] [PMID: 18060033]
[31]
d’Hennezel E, Kornete M, Piccirillo CA. IL-2 as a therapeutic target for the restoration of Foxp3+ regulatory T-cell function in organ-specific autoimmunity: Implications in pathophysiology and translation to human disease. J Transl Med 2010; 8(1): 113.
[http://dx.doi.org/10.1186/1479-5876-8-113] [PMID: 21059266]
[32]
Alhadj Ali M, Liu YF, Arif S, et al. Metabolic and immune effects of immunotherapy with proinsulin peptide in human new-onset type 1 diabetes. Sci Transl Med 2017; 9(402): eaaf7779.
[http://dx.doi.org/10.1126/scitranslmed.aaf7779] [PMID: 28794283]
[33]
Nambam B, Haller MJ. Updates on immune therapies in type 1 diabetes. Eur Endocrinol 2016; 12(2): 89-95.
[http://dx.doi.org/10.17925/EE.2016.12.02.89] [PMID: 29632594]
[34]
Long SA, Thorpe J, DeBerg HA, et al. Partial exhaustion of CD8 T-cells and clinical response to teplizumab in new-onset type 1 diabetes. Sci Immunol 2016; 1(5): eaai7793.
[http://dx.doi.org/10.1126/sciimmunol.aai7793] [PMID: 28664195]
[35]
Dolgin E. Anti-CD3 drug keeps diabetes at bay. Nat Biotechnol 2019; 37(10): 1099-101.
[http://dx.doi.org/10.1038/d41587-019-00025-4] [PMID: 31578500]
[36]
Stifter K, Schuster C, Schlosser M, Boehm BO, Schirmbeck R. Exploring the induction of preproinsulin-specific Foxp3+ CD4+ Treg cells that inhibit CD8+ T-cell-mediated autoimmune diabetes by DNA vaccination. Sci Rep 2016; 6(1): 29419.
[http://dx.doi.org/10.1038/srep29419] [PMID: 27406624]
[37]
Abdel-Moneim A, Bakery HH, Allam G. The potential pathogenic role of IL-17/Th17 cells in both type 1 and type 2 diabetes mellitus. Biomed Pharmacother 2018; 101: 287-92.
[http://dx.doi.org/10.1016/j.biopha.2018.02.103] [PMID: 29499402]
[38]
Klein L, Robey EA, Hsieh CS. Central CD4+ T-cell tolerance: Deletion versus regulatory T-ell differentiation. Nat Rev Immunol 2019; 19(1): 7-18.
[http://dx.doi.org/10.1038/s41577-018-0083-6] [PMID: 30420705]
[39]
Monaco C, Nanchahal J, Taylor P, Feldmann M. Anti-TNF therapy: Past, present and future. Int Immunol 2015; 27(1): 55-62.
[http://dx.doi.org/10.1093/intimm/dxu102] [PMID: 25411043]
[40]
Palladino MA, Bahjat FR, Theodorakis EA, Moldawer LL. Anti-TNF-α therapies: The next generation. Nat Rev Drug Discov 2003; 2(9): 736-46.
[http://dx.doi.org/10.1038/nrd1175] [PMID: 12951580]
[41]
Faustman DL. TNF, TNF inducers, and TNFR2 agonists: A new path to type 1 diabetes treatment. Diabetes Metab Res Rev 2018; 34(1): e2941.
[http://dx.doi.org/10.1002/dmrr.2941] [PMID: 28843039]
[42]
Peters MJL, Yu J, Behrens T, et al. Etanercept treatment in children with new-onset type 1 diabetes: Pilot randomized, placebo-controlled, double-blind study: Response to Mastrandrea et al. Diabetes Care 2009; 32(12): e153.
[http://dx.doi.org/10.2337/dc09-1372] [PMID: 19940216]
[43]
Martelli MF, Di Ianni M, Ruggeri L, et al. HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse. Blood 2014; 124(4): 638-44.
[http://dx.doi.org/10.1182/blood-2014-03-564401] [PMID: 24923299]
[44]
Dong D, Zheng L, Lin J, et al. Structural basis of assembly of the human T-cell receptor–CD3 complex. Nature 2019; 573(7775): 546-52.
[http://dx.doi.org/10.1038/s41586-019-1537-0] [PMID: 31461748]
[45]
Wang X, Ni L, Chang D, et al. Cyclic AMP-responsive element-binding protein (CREB) is critical in autoimmunity by promoting Th17 but inhibiting treg cell differentiation. EBioMedicine 2017; 25: 165-74.
[http://dx.doi.org/10.1016/j.ebiom.2017.10.010] [PMID: 29050947]
[46]
Kitashima DY, Kobayashi T, Woodring T, et al. Langerhans cells prevent autoimmunity via expansion of keratinocyte antigen-specific regulatory T-cells. EBioMedicine 2018; 27: 293-303.
[http://dx.doi.org/10.1016/j.ebiom.2017.12.022] [PMID: 29307572]
[47]
Boardman DA, Levings MK. Cancer immunotherapies repurposed for use in autoimmunity. Nat Biomed Eng 2019; 3(4): 259-63.
[http://dx.doi.org/10.1038/s41551-019-0359-6] [PMID: 30952977]
[48]
Tack CJ, Kleijwegt FS, Van Riel PLCM, Roep BO. Development of type 1 diabetes in a patient treated with anti-TNF-α therapy for active rheumatoid arthritis. Diabetologia 2009; 52(7): 1442-4.
[http://dx.doi.org/10.1007/s00125-009-1381-0] [PMID: 19440690]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy