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Monoklonal Antikor Teknolojisinin Dünü, Bugünü Ve Geleceği

Year 2016, Volume: 2 Issue: 1, 6 - 14, 31.01.2016
https://doi.org/10.30934/kusbed.358477

Abstract

20. yy başlarında Paul Erlich “sihirli mermi” (magic bullet) teorisini öne sürdüğünde elinde yalnızca Emil von Behring ile Kitasato Shibasaburō’nın hümoral immünitenin varlığına dair yapmış oldukları çalışmanın verileri mevcuttu. O günlerde antikorların varlığına dair hiçbir somut veri bulunmamaktaydı. Teoriye göre “eğer spesifik bir patojene özgü bir bileşik geliştirilebilirse, bu yolla söz konusu patojene toksin de gönderilebilirdi”. Bu bağlamda 80’lerden günümüze monoklonal antikor geliştirme teknolojisi alanında geldiğimiz nokta değerlendirildiğinde, Paul Erlich’in o yıllarda prensip olarak öne sürdüğü savaşım stratejisini hayata geçirebilecek teknolojinin ötesine geçmeye başladığımız söylenebilir. İlk yıllarda tamamı ile fare antikorlarının üretimi ile başlayan süreç, aynı yıllarda temelleri atılan rekombinant DNA teknolojisinin de yardımı ile büyük bir hızla gelişim göstermiştir. Günümüzde, proteomiks ve biyoinformatik alanlarının da söz konusu alanda varlık göstermeleri ile farklı organizmalarda bulunan daha uzun yarı-ömürlü antikorların insan zincirli versiyonlarından, çok fonksiyonlu antikorlara; toksin konjuge edilmiş antikor formlarından, radikal sayılabilecek tasarımlara kadar Paul Erlich’in hayallerinin çok ötesinde “sihirli mermiler” üretebilmekteyiz. Üstelik üretebildiğimiz bu mermiler tamamı ile hedefine özgüdür. Ancak bütün bu gelişmelere rağmen, güncel antikor geliştirme tekniklerinin getirdiği bazı kısıtlar nedeni ile olası salgınlarda yeterince hızlı davranamamakta; kanser vakalarında ise halen büyük ölçüde konvansiyonel silahlarımıza başvurmak zorunda kalmaktayız. Neyse ki söz konusu alandaki hızlı gelişim ve günümüzde mevcut olan teknolojik olanaklar nedeni ile monoklonal antikor teknolojisinin çeyrek asırda kat ettiği yolun çok daha fazlasını önümüzdeki 10-20 yıl içinde kat etmesi beklenmektedir. Bu bağlamda, günümüz dünya ilaç pazarındaki payı %25’ten fazla olan protein bazlı biyoteknolojik ilaçların, yakın bir gelecekte kimyasal olarak sentezlenen konvansiyonel terapötiklerin yerini alarak pazarın büyük çoğunluğuna hakim olması beklenmektedir.

References

  • Selimoglu SM ve Elibol M. Alginate as an immobilization material for MAbproduction via encapsulate hybridoma cells. Critical Reviews in Biotechnology. 2010; 30(2): 145-59.
  • Mallery DL, McEwan WA, Bidgood SR, Towers GJ, Johnson CM ve James LC.Antibodies mediate intracellular immunity through tripartite motif-containing 21(TRIM21). PNAS. 2010; 107(46): 19985–90.
  • Roopenian DC ve Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nature Reviews Immunology. 2007; 7: 715-25.
  • Köhler GJ ve Milstein C. Continuous cultures of fused cells secreting antibody ofpredefined specificity. Nature. 1975; 256(5517): 495-97.
  • Greenfield EA. Generating Monoclonal Antibodies. İçinde Antibodies: ALaboratory Manual, 2. Baskı, Cold Spring Harbor Laboratory Press, 2014; s. 205-207.
  • Ecker DM, Jones SD ve Levine HL. The therapeutic monoclonal antibody market. mAbs. 2015; 7(1): 9-14.
  • Candaş D. Düşmanlarımızın ürettiği dostlar: monoklonal antikorlar. Bilim veTeknik. 2002; 410: 50-54.
  • Chames P ve Baty D. Bispecific antibodies for cancer therapy. The light at the end of the tunnel?. MAbs. 2009; 6(1): 539-47.
  • Diagram of an Antibody, Novimmune. 15 Kasım 2015’tehttp://www.novimmune.com/science/antibodies.html adresinden indirildi. (ulaşımaaçık kaynaktır).
  • Nelson AL, Dhimolea E ve Reichert JM. Development trends for humanmonoclonal antibody therapeutics. Nature Reviews. 2010; 9: 767-74.
  • Ni J. New Technologies for the Generation of Human Monoclonal Antibody.Trends in Biopharmaceutical Industry. 2009; 5(3): 3-12.
  • Frenzel A, Hust M ve Schirrmann T. Expression of recombinant antibodies.Frontiers in Immunology. 2013; 4(217): 1-20.
  • Todorovska A, Roovers RC, Dolezal O, Kortt AA, Hoogenboom HR ve HudsonPJ. Design and application of diabodies, triabodies and tetrabodies. Journal ofImmunological Methods. 2001; 248: 47-66.
  • Holliger P ve Hudson PJ. Engineered antibody fragments and the rise of singledomains. Nature Biotechnolog. 2005; 23(9): 1126-36.
  • Kierny MR, Cunningham TD ve Kay BK. Detection of biomarkers usingrecombinant antibodies coupled to nanostructured platforms. Nano Reviews. 2012;3: 17240 - http://dx.doi.org/10.3402/nano.v3i0.17240
  • Brekke OH ve Sandlie I. Therapeutic antibodies for human diseases at the down of the twenty-first century. Nature Reviews. 2003; 2: 52-62.
  • Jakobovits A. Production of fully human antibodies by transgenic mice. Current Opinion in Biotechnology. 1995; 6: 561-66.
  • Traggiai E, Becker S, Subbarao K, Kolesnikova L, Uematsu Y, Gismondo MR,Murphy BR, Rappuoli R ve Lanzavecchia A. An efficient method to make humanmonoclonal antibodies from memory B cells: potent neutralization of SARScoronavirus. Nature Medicine. 2004; 10: 871-75.
  • Smith SA ve Crowe JE. Use of human hybridoma technology to isolate humanmonoclonal antibodies. Microbiology Spectrum. 2015; 3(1): 1-12.
  • Karpas A, Dremucheva A ve Czepulkowski BH. A human myeloma cell linesuitable for the generation of human monoclonal antibodies. Proc Natl Acad SciUSA. 2001; 98(4): 1799–1804.
  • Dohmen SE, Mulder A, Verhagen OJ, Eijsink C, Dijk MEFv ve Schoot CEvd.Production of recombinant Ig molecules from antigen-selected single B cells andrestricted usage of Ig-gene segments by anti-D antibodies. J Immunol Methods.2005; 298(1-2): 9-20.
  • Teng NN, Lam KS, Riera FC ve Kaplan HS. Construction and testing of mouse--human heteromyelomas for human monoclonal antibody production. Proc. Natl.Acad. Sci. USA. 1983; 80(23): 7308-12.
  • Gorny MK, Xu JY, Karwowska S, Buchbinder A ve Zolla-Pazner S. Repertoire of neutralizing human monoclonal antibodies specific for the V3 domain of HIV-1 gp120. J Immunol. 1993; 150(2): 635-43.
  • Gorny MK, Wang XH, Williams C, Volsky B, Revesz K, Witover B, Burda S,Urbanski M, Nyambi P, Krachmarov C, Pinter A, Zolla-Pazner S ve Nadas A.Preferential use of the VH5-51 gene segment by the human immune response tocode for antibodies against the V3 domain of HIV-1. Mol Immunol. 2009; 46: 917-26.
  • Gorny, MK. Human hybridoma technology. Antibody Technol J. 2012; 2: 1-5.
  • Yu X, McGraw PA, House FS ve Crowe JEJ. An optimized electrofusion-based protocol for generating virus-specific human monoclonal antibodies. J ImmunolMethods. 2008; 336: 142-51.
  • da Silva Cardoso M, Siemoneit K, Sturm D, Krone C, Moradpour D ve KubanekB. Isolation and characterization of human monoclonal antibodies against hepatitis C virus envelope glycoproteins. J Med Virol. 1998; 55: 28-34.
  • Ogura M, Morishima Y, Ohno R, Kato Y, Hirabayashi N, Nagura H ve Saito H.Establishment of a novel human megakaryoblastic leukemia cell line, MEG-01, with positive Philadelphia chromosome. Blood. 1985; 66: 1384-92.
  • Dessain SK, Adekar SP, Stevens JB, Carpenter KA, Skorski ML, Barnoski BL,Goldsby RA ve Weinberg RA. High efficiency creation of human monoclonalantibody-producing hybridomas. J Immunol Methods. 2004; 291: 109-22.

Yesterday, Today And The Future Of Monoclonal Antibody Technology

Year 2016, Volume: 2 Issue: 1, 6 - 14, 31.01.2016
https://doi.org/10.30934/kusbed.358477

Abstract

When Paul Erlich postulated the idea of “magic bullet” in the early part of 20th century, he only had the findings of a research, regarding the presence of humoral immunity, performed by Emil von Behring and Kitasato Shibasaburo.. There was no concrete data about the presence of antibodies in those days. According to the idea, “if a compound could be made that selectively targeted a disease-causing organism, then a toxin for that organism could be delivered along with the agent of selectivity”. If the point in the technology of monoclonal antibody generation that we have reached from ‘80s to present is considered, it can be claimed that we have started to go beyond the technology realizing the fighting strategy principally proposed by Paul Erlich at those times. The period starting with the production of fully murine antibodies in the first years exhibited a fast-growing trend with the help of recombinant DNA technology established around the same years. Today, we can generate various “magic bullets”, being so much beyond what Paul Erlich might dream, with the contributions of fields such as proteomics and bioinformatics. Those range from human-chained antibodies found in different species with longer half-life to multifunctional antibody forms, and from toxin-conjugated antibodies to novel designs, which may be considered as radical. Furthermore, the bullets that we can produce are completely target-specific. In spite of all these developments, we cannot take actions sufficiently fast due to some constraints of recent antibody development techniques. In cancer cases, we are still mostly obliged to resort to our conventional guns. Fortunately, monoclonal antibody technology is expected to make much more progress within 10-20 years than it has made in the past quarter-century because of rapid progress in the field and current technological capabilities. Thus, protein-based biotechnological drugs, of which current global market share is more than 25%, are expected to substitute most chemical-based conventional therapeutics and dominate most of the market in the near future.

References

  • Selimoglu SM ve Elibol M. Alginate as an immobilization material for MAbproduction via encapsulate hybridoma cells. Critical Reviews in Biotechnology. 2010; 30(2): 145-59.
  • Mallery DL, McEwan WA, Bidgood SR, Towers GJ, Johnson CM ve James LC.Antibodies mediate intracellular immunity through tripartite motif-containing 21(TRIM21). PNAS. 2010; 107(46): 19985–90.
  • Roopenian DC ve Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nature Reviews Immunology. 2007; 7: 715-25.
  • Köhler GJ ve Milstein C. Continuous cultures of fused cells secreting antibody ofpredefined specificity. Nature. 1975; 256(5517): 495-97.
  • Greenfield EA. Generating Monoclonal Antibodies. İçinde Antibodies: ALaboratory Manual, 2. Baskı, Cold Spring Harbor Laboratory Press, 2014; s. 205-207.
  • Ecker DM, Jones SD ve Levine HL. The therapeutic monoclonal antibody market. mAbs. 2015; 7(1): 9-14.
  • Candaş D. Düşmanlarımızın ürettiği dostlar: monoklonal antikorlar. Bilim veTeknik. 2002; 410: 50-54.
  • Chames P ve Baty D. Bispecific antibodies for cancer therapy. The light at the end of the tunnel?. MAbs. 2009; 6(1): 539-47.
  • Diagram of an Antibody, Novimmune. 15 Kasım 2015’tehttp://www.novimmune.com/science/antibodies.html adresinden indirildi. (ulaşımaaçık kaynaktır).
  • Nelson AL, Dhimolea E ve Reichert JM. Development trends for humanmonoclonal antibody therapeutics. Nature Reviews. 2010; 9: 767-74.
  • Ni J. New Technologies for the Generation of Human Monoclonal Antibody.Trends in Biopharmaceutical Industry. 2009; 5(3): 3-12.
  • Frenzel A, Hust M ve Schirrmann T. Expression of recombinant antibodies.Frontiers in Immunology. 2013; 4(217): 1-20.
  • Todorovska A, Roovers RC, Dolezal O, Kortt AA, Hoogenboom HR ve HudsonPJ. Design and application of diabodies, triabodies and tetrabodies. Journal ofImmunological Methods. 2001; 248: 47-66.
  • Holliger P ve Hudson PJ. Engineered antibody fragments and the rise of singledomains. Nature Biotechnolog. 2005; 23(9): 1126-36.
  • Kierny MR, Cunningham TD ve Kay BK. Detection of biomarkers usingrecombinant antibodies coupled to nanostructured platforms. Nano Reviews. 2012;3: 17240 - http://dx.doi.org/10.3402/nano.v3i0.17240
  • Brekke OH ve Sandlie I. Therapeutic antibodies for human diseases at the down of the twenty-first century. Nature Reviews. 2003; 2: 52-62.
  • Jakobovits A. Production of fully human antibodies by transgenic mice. Current Opinion in Biotechnology. 1995; 6: 561-66.
  • Traggiai E, Becker S, Subbarao K, Kolesnikova L, Uematsu Y, Gismondo MR,Murphy BR, Rappuoli R ve Lanzavecchia A. An efficient method to make humanmonoclonal antibodies from memory B cells: potent neutralization of SARScoronavirus. Nature Medicine. 2004; 10: 871-75.
  • Smith SA ve Crowe JE. Use of human hybridoma technology to isolate humanmonoclonal antibodies. Microbiology Spectrum. 2015; 3(1): 1-12.
  • Karpas A, Dremucheva A ve Czepulkowski BH. A human myeloma cell linesuitable for the generation of human monoclonal antibodies. Proc Natl Acad SciUSA. 2001; 98(4): 1799–1804.
  • Dohmen SE, Mulder A, Verhagen OJ, Eijsink C, Dijk MEFv ve Schoot CEvd.Production of recombinant Ig molecules from antigen-selected single B cells andrestricted usage of Ig-gene segments by anti-D antibodies. J Immunol Methods.2005; 298(1-2): 9-20.
  • Teng NN, Lam KS, Riera FC ve Kaplan HS. Construction and testing of mouse--human heteromyelomas for human monoclonal antibody production. Proc. Natl.Acad. Sci. USA. 1983; 80(23): 7308-12.
  • Gorny MK, Xu JY, Karwowska S, Buchbinder A ve Zolla-Pazner S. Repertoire of neutralizing human monoclonal antibodies specific for the V3 domain of HIV-1 gp120. J Immunol. 1993; 150(2): 635-43.
  • Gorny MK, Wang XH, Williams C, Volsky B, Revesz K, Witover B, Burda S,Urbanski M, Nyambi P, Krachmarov C, Pinter A, Zolla-Pazner S ve Nadas A.Preferential use of the VH5-51 gene segment by the human immune response tocode for antibodies against the V3 domain of HIV-1. Mol Immunol. 2009; 46: 917-26.
  • Gorny, MK. Human hybridoma technology. Antibody Technol J. 2012; 2: 1-5.
  • Yu X, McGraw PA, House FS ve Crowe JEJ. An optimized electrofusion-based protocol for generating virus-specific human monoclonal antibodies. J ImmunolMethods. 2008; 336: 142-51.
  • da Silva Cardoso M, Siemoneit K, Sturm D, Krone C, Moradpour D ve KubanekB. Isolation and characterization of human monoclonal antibodies against hepatitis C virus envelope glycoproteins. J Med Virol. 1998; 55: 28-34.
  • Ogura M, Morishima Y, Ohno R, Kato Y, Hirabayashi N, Nagura H ve Saito H.Establishment of a novel human megakaryoblastic leukemia cell line, MEG-01, with positive Philadelphia chromosome. Blood. 1985; 66: 1384-92.
  • Dessain SK, Adekar SP, Stevens JB, Carpenter KA, Skorski ML, Barnoski BL,Goldsby RA ve Weinberg RA. High efficiency creation of human monoclonalantibody-producing hybridomas. J Immunol Methods. 2004; 291: 109-22.
There are 29 citations in total.

Details

Subjects Health Care Administration
Journal Section Review Article
Authors

S: Mert Selimoğlu This is me

Murat Kasap This is me

Gürler Akpınar

Aynur Karadenizli

Publication Date January 31, 2016
Submission Date November 24, 2015
Acceptance Date December 27, 2015
Published in Issue Year 2016 Volume: 2 Issue: 1

Cite

APA Selimoğlu, S. M., Kasap, M., Akpınar, G., Karadenizli, A. (2016). Monoklonal Antikor Teknolojisinin Dünü, Bugünü Ve Geleceği. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi, 2(1), 6-14. https://doi.org/10.30934/kusbed.358477
AMA Selimoğlu SM, Kasap M, Akpınar G, Karadenizli A. Monoklonal Antikor Teknolojisinin Dünü, Bugünü Ve Geleceği. KOU Sag Bil Derg. January 2016;2(1):6-14. doi:10.30934/kusbed.358477
Chicago Selimoğlu, S: Mert, Murat Kasap, Gürler Akpınar, and Aynur Karadenizli. “Monoklonal Antikor Teknolojisinin Dünü, Bugünü Ve Geleceği”. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi 2, no. 1 (January 2016): 6-14. https://doi.org/10.30934/kusbed.358477.
EndNote Selimoğlu SM, Kasap M, Akpınar G, Karadenizli A (January 1, 2016) Monoklonal Antikor Teknolojisinin Dünü, Bugünü Ve Geleceği. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi 2 1 6–14.
IEEE S. M. Selimoğlu, M. Kasap, G. Akpınar, and A. Karadenizli, “Monoklonal Antikor Teknolojisinin Dünü, Bugünü Ve Geleceği”, KOU Sag Bil Derg, vol. 2, no. 1, pp. 6–14, 2016, doi: 10.30934/kusbed.358477.
ISNAD Selimoğlu, S: Mert et al. “Monoklonal Antikor Teknolojisinin Dünü, Bugünü Ve Geleceği”. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi 2/1 (January 2016), 6-14. https://doi.org/10.30934/kusbed.358477.
JAMA Selimoğlu SM, Kasap M, Akpınar G, Karadenizli A. Monoklonal Antikor Teknolojisinin Dünü, Bugünü Ve Geleceği. KOU Sag Bil Derg. 2016;2:6–14.
MLA Selimoğlu, S: Mert et al. “Monoklonal Antikor Teknolojisinin Dünü, Bugünü Ve Geleceği”. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi, vol. 2, no. 1, 2016, pp. 6-14, doi:10.30934/kusbed.358477.
Vancouver Selimoğlu SM, Kasap M, Akpınar G, Karadenizli A. Monoklonal Antikor Teknolojisinin Dünü, Bugünü Ve Geleceği. KOU Sag Bil Derg. 2016;2(1):6-14.