Skip to main content
SpringerLink
Log in

Targets of monoclonal antibodies for immunological diseases

  • Review
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Immunological disorders such as allergy, autoimmune diseases, auto-inflammatory syndromes and immunological deficiency syndromes are difficult to treat with chemical drugs. Recently, many monoclonal antibodies targeting various molecules including interleukin, tumor necrosis factor-α, cluster of differentiation, integrins, complement C5 and B lymphocyte stimulator are clinically available and give a hope to patients suffering from these intractable diseases. Here, we selected twenty-seven monoclonal antibodies approved by US FDA since 1997 and they are classified according to their target molecules. Although these biomedicines possessed some restrictions such as high cost and susceptible to infectious disease, these drawbacks can be overcome through cost-cutting innovations including biosimilars and careful monitoring. New targets are emerging rapidly and more effective biomedicines with acceptable side effects are in the pipeline for next decade.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Al-Ramli W, Préfontaine D, Chouiali F, Martin JG, Olivenstein R, Lemière C, Hamid Q (2009) TH17-associated cytokines (IL-17A and IL-17F) in severe asthma. J Allergy Clin Immunol 123:1185–1187

    Article  CAS  PubMed  Google Scholar 

  • Berger A (2000) Th1 and Th2 responses: what are they? BMJ 321:424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonifant CL, Jackson HJ, Brentjens RJ, Curran KJ (2016) Toxicity and management in CAR T-cell therapy. Mol Ther Oncolytics 3:16011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burmester GR, Lin Y, Patel R, van Adelsberg J, Mangan EK, Graham NMH, van Hoogstraten H, Bauer D, Vargas JI, Lee EB (2016) Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis 76:840–847

    Article  CAS  PubMed  Google Scholar 

  • Cancro MP, D’Cruz DP, Khamashta MA (2009) The role of B lymphocyte stimulator (BLyS) in systemic lupus erythematosus. J Clin Invest 119:1066–1073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chatzidionysiou K, Lie E, Nasanov E, Lukina G, Hetland ML, Tarp U, Gabay C, van Riel PL, Nordström DC, Gomez-Reino J, Pavelka K, Tomsic M, Kvien TK, van Vollenhoven RF (2011) Highest clinical effectiveness of rituximab in autoantibody-positive patients with rheumatoid arthritis and in those for whom no more than one previous TNF antagonist has failed. Ann Rheum Dis 70:1575–1580

    Article  CAS  PubMed  Google Scholar 

  • Chen R, Chen B (2015) Siltuximab (CNTO 328): a promising option for human malignancies. Drug Des Devel Ther 9:3455–3458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen JB, Wu PC, Hung AF, Chu CY, Tsai TF, Yu HM, Chang HY, Chang TW (2010) Unique epitopes on C epsilon mX in IgE-B cell receptors are potentially applicable for targeting IgE-committed B cells. J Immunol 184:1748–1756

    Article  CAS  PubMed  Google Scholar 

  • Cohen MD, Keystone E (2015) Rituximab for rheumatoid arthritis. Rheumatol Ther 2:99–111

    Article  PubMed  PubMed Central  Google Scholar 

  • Conner J, Wuchterl D, Lopez M, Minshall B, Prusti R, Boclair D, Peterson J, Allen C (2014) Chapter 26; the biomanufacturing of biotechnology products; biotechnology entrepreneurship, 1st edn. Elsevier, Oxford, pp 351–385

    Google Scholar 

  • Deisseroth A, Ko CW, Nie L, Zirkelbach JF, Zhao L, Bullock J, Mehrotra N, Del Valle P, Saber H, Sheth C, Gehrke B, Justice R, Farrell A, Pazdur R (2015) FDA approval: siltuximab for the treatment of patients with multicentric Castleman disease. Clin Cancer Res 21:950–954

    Article  CAS  PubMed  Google Scholar 

  • Dhillon S (2018) Eculizumab: a review in generalized myasthenia gravis. Drugs 78:367–376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Di Cesare A, Di Meglio P, Nestle FO (2009) The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol 129:1339–1350

    Article  CAS  PubMed  Google Scholar 

  • Dinarello CA (1991) Inflammatory cytokines: interleukin-1 and tumor necrosis factor as effector molecules in autoimmune diseases. Curr Opin Immunol 3:941–948

    Article  CAS  PubMed  Google Scholar 

  • Doran E, Cai F, Holweg CTJ, Wong K, Brumm J, Arron JR (2017) Interleukin-13 in asthma and other eosinophilic disorders. Front Med 4:139

    Article  Google Scholar 

  • Eberle FC, Brück J, Holstein J, Hirahara K, Ghoreschi K (2016) Recent advances in understanding psoriasis. F1000Research p.5

  • FDA (2017) News release: Press Announcements-FDA approves first drug for Eosinophilic Granulomatosis with Polyangiitis, a rare disease formerly known as the Churg-Strauss Syndrome. Accessed 11 July 2018

  • Fitch E, Harper E, Skorcheva I, Kurtz SE, Blauvelt A (2007) Pathophysiology of psoriasis: recent advances on IL-23 and Th17 cytokines. Curr Rheumatol Rep 9:461–467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Focosi D, Maggi F, Pistello M, Boggi U, Scatena F (2011) Immunosuppressive monoclonal antibodies: current and next generation. Clin Microbiol Infect 17:1759–1768

    Article  CAS  PubMed  Google Scholar 

  • Gabay C, Emery P, van Vollenhoven R, Dikranian A, Alten R, Pavelka K, Klearman M, Musselman D, Agarwal S, Green J, Kavanaugh A, ADACTA Study Investigators (2013) Tocilizumab monotherapy versus adalimumab monotherapy for treatment of rheumatoid arthritis (ADACTA): a randomised, double-blind, controlled phase 4 trial. Lancet 381:1541–1550

    Article  CAS  PubMed  Google Scholar 

  • Galli SJ, Tsai M (2012) IgE and mast cells in allergic disease. Nat Med 18:693–704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gould HJ, Sutton BJ, Beavil AJ, Beavil RL, McCloskey N, Coker HA, Fear D, Smurthwaite L (2003) The biology of IGE and the basis of allergic disease. Annu Rev Immunol 21:579–628

    Article  CAS  PubMed  Google Scholar 

  • Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A (2017) Ocrelizumab versus Interferon beta-1a in relapsing multiple sclerosis. N Engl J Med 376:221–234

    Article  CAS  PubMed  Google Scholar 

  • Hooks MA, Wade CS, Milikan WJ (1991) Muromonab CD-3: a review of its pharmacology, pharmacokinetics, and clinical use in transplantation. Pharmacotherapy 11:26–37

    CAS  PubMed  Google Scholar 

  • Howard JF Jr (2018) Myasthenia gravis: the role of complement at the neuromuscular junction. Ann N Y Acad Sci 1412:113–128

    Article  CAS  PubMed  Google Scholar 

  • Isaacs JD, Cohen SB, Mery P, Tak PP, Wang J, Lei G, Williams S, Lal P, Read SJ (2013) Effect of baseline rheumatoid factor and anti-citrullinated peptide antibody serotype on rituximab clinical response: a meta-analysis. Ann Rheum Dis 72:329–336

    Article  CAS  PubMed  Google Scholar 

  • Jakimovski D, Weinstock-Guttman B, Ramanathan M, Kolb C, Hojnacki D, Minagar A, Zivadinov R (2017) Ocrelizumab: a B-cell depleting therapy for multiple sclerosis. Expert Opin Biol Ther 17:1163–1172

    Article  CAS  PubMed  Google Scholar 

  • Johnson CY (2017) Major drug study opens up vast new opportunities in combating heart disease. The Washington Post. Accessed 30 Aug 2017

  • Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497

    Article  PubMed  Google Scholar 

  • Kreuzaler M, Rauch M, Salzer U, Birmelin J, Rizzi M, Grimbacher B, Plebani A, Lougaris V, Quinti I, Thon V, Litzman J, Schlesier M, Warnatz K, Thiel J, Rolink AG, Eibel H (2012) Soluble BAFF levels inversely correlate with peripheral B cell numbers and the expression of BAFF receptors. J Immunol 188:497–503

    Article  CAS  PubMed  Google Scholar 

  • Lal P, Su Z, Holweg CT, Silverman GJ, Schwartzman S, Kelman A, Read S, Spaniolo G, Monroe JG, Behrens TW, Townsend MJ (2011) Inflammation and autoantibody markers identify rheumatoid arthritis patients with enhanced clinical benefit following rituximab treatment. Arthritis Rheum 63:3681–3691

    Article  CAS  PubMed  Google Scholar 

  • Larochelle C, Alvarez JI, Prat A (2011) How do immune cells overcome the blood-brain barrier in multiple sclerosis? FEBS Lett 585:3770–3780

    Article  CAS  PubMed  Google Scholar 

  • Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA (2004) New insights into atopic dermatitis. J Clin Invest 113:651–657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leung S, Liu X, Fang L, Chen X, Guo T, Zhang J (2010) The cytokine milieu in the interplay of pathogenic Th1/Th17 cells and regulatory T cells in autoimmune disease. Cell Mol Immunol 7:182–189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ley K, Rivera-Nieves J, Sandborn WJ, Shattil S (2016) Integrin-based therapeutics: biological basis, clinical use and new drugs. Nat Rev Drug Discov 15:173–183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin PL, Plessner HL, Voitenok NN, Flynn JL (2007) Tumor necrosis factor and tuberculosis. J Investig Dermatol Symp Proc 12:22–25

    Article  CAS  PubMed  Google Scholar 

  • Lis K, Kuzawińska O, Bałkowiec-Iskra E (2014) Tumor necrosis factor inhibitors—state of knowledge. Arch Med Sci 10:1175–1185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loma I, Heyman R (2011) Multiple sclerosis: pathogenesis and treatment. Curr Neuropharmacol 9:409–416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lønnberg AS, Zachariae C, Skov L (2014) Targeting of interleukin-17 in the treatment of psoriasis. Clin Cosmet Investig Dermatol 7:251–259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luzzatto L, Risitano AM, Notaro R (2010) Paroxysmal nocturnal hemoglobinuria and eculizumab. Haematologica 95:523–526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malerich P, Elston DM (2006) Introduction of TNF/Pathophysiology of TNF. In: Weinberg JM, Buholtz R (eds) TNF-alpha inhibitors. Birkhäuser Verlag, Basel, pp 1–8

    Google Scholar 

  • March CJ, Mosley B, Larsen A, Cerretti DP, Braedt G, Price V, Gillis S, Henney CS, Kronheim SR, Grabstein K (1985) Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature 315:641–647

    Article  CAS  PubMed  Google Scholar 

  • Maus MV, June CH (2016) Making better chimeric antigen receptors for adoptive T-cell therapy. Clin Cancer Res 22:1875–1884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • May RD, Fung M (2015) Strategies targeting the IL-4/IL-13 axes in disease. Cytokine 75:89–116

    Article  CAS  PubMed  Google Scholar 

  • McBrien CN, Menzies-Gow A (2017) The biology of eosinophils and their role in asthma. Front Med 4:93

    Article  Google Scholar 

  • Miossec P, Kolls JK (2012) Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov 11:763–776

    Article  CAS  PubMed  Google Scholar 

  • Moudgil KD, Choubey D (2011) Cytokines in autoimmunity: role in induction, regulation, and treatment. J Interferon Cytokine Res 31:695–703

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, Barker P, Sproule S, Ponnarambil S, Goldman M (2017) Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med 376:2448–2458

    Article  CAS  PubMed  Google Scholar 

  • Navarra SV, Guzmán RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, Li EK, Thomas M, Kim HY, León MG, Tanasescu C, Nasonov E, Lan JL, Pineda L, Zhong ZJ, Freimuth W, Petri MA (2011) Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 377:721–731

    Article  CAS  PubMed  Google Scholar 

  • Nicholson LB (2016) The immune system. Essays Biochem 60:275–301

    Article  PubMed  PubMed Central  Google Scholar 

  • Nixon J, Newbold P, Mustelin T, Anderson GP, Kolbeck R (2017) Monoclonal antibody therapy for the treatment of asthma and chronic obstructive pulmonary disease with eosinophilic inflammation. Pharmacol Ther 169:57–77

    Article  CAS  PubMed  Google Scholar 

  • Noack M, Miossec P (2014) Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun Rev 13:668–677

    Article  CAS  PubMed  Google Scholar 

  • Panettieri RA Jr, Wang M, Braddock M, Bowen K, Colice G (2018) Tralokinumab for the treatment of severe, uncontrolled asthma: the ATMOSPHERE clinical development program. Immunotherapy 10:473–490

    Article  CAS  PubMed  Google Scholar 

  • Parameswaran N, Patial S (2010) Tumor necrosis factor-α signaling in macrophages. Crit Rev Eukaryot Gene Expr 20:87–103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parker C (2009) Eculizumab for paroxysmal nocturnal haemoglobinuria. Lancet 373:759–767

    Article  CAS  PubMed  Google Scholar 

  • Rider P, Carmi Y, Cohen I (2016) Biologics for targeting inflammatory cytokines, clinical uses, and limitations. Int J Cell Biol 2016:9259646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ross JA, Auger MJ (2002) The biology of the macrophage. In: Burke B, Lewis CE (eds) The macrophage, 2nd edn. Oxford University Press Inc., New York

    Google Scholar 

  • Salvana EMT, Salata RA (2009) Infectious complications associated with monoclonal antibodies and related small molecules. Clin Microbiol Rev 22:274–290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schlesinger M, Bendas G (2015) Contribution of very late antigen-4 (VLA-4) integrin to cancer progression and metastasis. Cancer Metastasis Rev 34:575–591

    Article  CAS  PubMed  Google Scholar 

  • Schroeder HW, Cavacini L (2010) Structure and function of immunoglobulins. J Allergy Clin Immunol 125:S41–S52

    Article  PubMed  PubMed Central  Google Scholar 

  • Scott LJ (2017) Tocilizumab: a review in rheumatoid arthritis. Drugs 77:1865–1879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shirley M (2017) Dupilumab: first global approval. Drugs 77:1115–1121

    Article  CAS  PubMed  Google Scholar 

  • Shirley M, Scott LJ (2016) Secukinumab: a review in psoriatic arthritis. Drugs 76:1135–1145

    Article  CAS  PubMed  Google Scholar 

  • Singh H, Grewal N, Arora E, Kumar H, Kakkar AK (2016a) Vedolizumab: a novel anti-integrin drug for treatment of inflammatory bowel disease. J Nat Sci Biol Med 7:4–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, Vaysbrot E, McNaughton C, Osani M, Shmerling RH, Curtis JR (2016b) 2015 American College of Rheumatology Guideline for the treatment of rheumatoid arthritis. Arthritis Rheumatol 68:1–26

    PubMed  Google Scholar 

  • Smolen JS, Emery P (2011) Infliximab: 12 years of experience. Arthritis Res Ther 13:S2

    PubMed  PubMed Central  Google Scholar 

  • Sorensen PS, Blinkenberg M (2016) The potential role for ocrelizumab in the treatment of multiple sclerosis: current evidence and future prospects. Ther Adv Neurol Disord 9:44–52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steinman L, Zamvil S (2003) Transcriptional analysis of targets in multiple sclerosis. Nat Rev Immunol 3:483–492

    Article  CAS  PubMed  Google Scholar 

  • Steri M, Orru V, Idda ML, Pitzalis M, Pala M, Zara I, Sidore C, Faà V, Floris M, Deiana M, Asunis L (2017) Overexpression of the cytokine BAFF and autoimmunity risk. N Engl J Med 376:1615–1626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tabarkiewicz J, Pogoda K, Karczmarczyk A, Pozarowski P, Giannopoulos K (2015) The Role of IL-17 and Th17 Lymphocytes in Autoimmune Diseases. Arch Immunol Ther Exp 63:435–449

    Article  CAS  Google Scholar 

  • Tan LD, Bratt JM, Godor D, Louie S, Kenyon NJ (2016) Benralizumab: a unique IL-5 inhibitor for severe asthma. J Asthma Allergy 9:71–81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanaka T, Ogata A, Narazaki M (2013) Tocilizumab: an updated review of its use in the treatment of rheumatoid arthritis and its application for other immune-mediated diseases. Clin Med Insights Ther 5:33–52

    CAS  Google Scholar 

  • Vasanthi P, Nalini G, Rajasekhar G (2007) Role of tumor necrosis factor-alpha in rheutomatoid arthritis: a review. APLAR J Rheumatol 10:270–274

    Article  Google Scholar 

  • Villiger PM, Adler S, Kuchen S, Felix W, Dan D, Fiege V, Butikofer L, Seitz M, Reichenbach S (2016) Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet 387:10031

    Article  CAS  Google Scholar 

  • Waite JC, Skokos D (2011) Th17 response and inflammatory autoimmune diseases. Int J Inflam 2012:819467

    PubMed  PubMed Central  Google Scholar 

  • Weiner GJ (2010) Rituximab: mechanism of action. Semin Hematol 47:115–123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wekell P, Karlsson A, Berg S, Fasth A (2016) Review of autoinflammatory diseases, with a special focus on periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome. Acta Paediatr 105:1140–1151

    Article  PubMed  PubMed Central  Google Scholar 

  • Wingerchuk DM, Lucchinetti CF, Noseworthy JH (2001) Multiple sclerosis: current pathophysiological concepts. Lab Invest 81:263–281

    Article  CAS  PubMed  Google Scholar 

  • Witsell AL, Schook LB (1992) Tumor necrosis factor alpha is an autocrine growth regulator during macrophage differentiation. Proc Natl Acad Sci USA 89:4754–4758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wong EKS, Kavanagh D (2018) Diseases of complement dysregulation—an overview. Semin Immunopathol 40:49–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wood BL, Arroz M, Barnett D, DiGiuseppe J, Greig B, Kussick SJ, Oldaker T, Shenkin M, Stone E, Wallace P (2007) 2006 Bethesda International Consensus recommendations on the immunophenotypic analysis of hematolymphoid neoplasia by flow cytometry: optimal reagents and reporting for the flow cytometric diagnosis of hematopoietic neoplasia. Cytometry B Clin Cytom 72:S14–S22

    Article  PubMed  Google Scholar 

  • Wu GF, Alvarez E (2011) The immuno-pathophysiology of multiple sclerosis. Neurol Clin 29:257–278

    Article  PubMed  PubMed Central  Google Scholar 

  • Yamasaki K, Taga T, Hirata Y, Yawata H, Kawanishi Y, Seed B, Taniguchi T, Hirano T, Kishimoto T (1988) Cloning and expression of human interleukin 6 (BSF-2/IFN b2) receptor. Science 241:825–828

    Article  CAS  PubMed  Google Scholar 

  • Yoshizaki K, Matsuda T, Nishimoto N, Kuritani T, Taeho L, Aozasa K, Nakahata T, Kawai H, Tagoh H, Komori T (1989) Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman’s disease. Blood 74:1360–1367

    CAS  PubMed  Google Scholar 

  • Yu JR, Leslie KS (2011) Cryopyrin-associated periodic syndrome: an update on diagnosis and treatment response. Curr Allergy Asthma Rep 11:12–20

    Article  CAS  PubMed  Google Scholar 

  • Zamorano J, Rivas M, Perez G (2003) Interleukin-4: a multifunctional cytokine. Immunologia 22:215–224

    Google Scholar 

  • Zhu J, Paul WE (2008) CD4 T cells: fates, functions, and faults. Blood 112:1557–1569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zola H, Swart B, Banham A, Barry S, Beare A, Bensussan A, Boumsell L, Buckley CD, Bunhring HS, Clark G, Engel P, Fox D, Jin BQ, Macardle PJ, Malavasi F, Mason D, Stockinger H, Yang X (2017) CD molecules 2006–human cell differentiation molecules. J Immunol Methods 319:1–5

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, College of Pharmacy, Kyung Hee University, 26 Kyungheedae-ro, Seoul, 02447, Republic of Korea

    Seon Min Yoo & Sung Hyun Chung

Authors
  1. Seon Min Yoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sung Hyun Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sung Hyun Chung.

Ethics declarations

Conflicts of interest

All contributing authors declare no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yoo, S.M., Chung, S.H. Targets of monoclonal antibodies for immunological diseases. Arch. Pharm. Res. 42, 293–304 (2019). https://doi.org/10.1007/s12272-018-1087-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-018-1087-2

Keywords

Search

Navigation