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Monoclonal Antibodies: Production, Techniques, and Global Marketing

Yıl 2022, Cilt: 3 Sayı: 1, 298 - 309, 07.04.2022

Öz

Monoclonal antibodies are becoming increasingly important for molecular immunology research. It has also become key components in a wide variety of clinical laboratory diagnostic tests. The wide applications of serum analytes in the detection and identification of cell markers and pathogenic agents have arisen in large part due to the excellent specificity of these unique reagents. Furthermore, continuous culture of hybridoma cells producing these antibodies offers the potential for an unlimited source of reagents. In essence, the continuous supply feature provides standardization of both reagent and assay technique, compared to the very limited supply of polyclonal antibody reagents. Clearly, polyclonal and monoclonal antibodies have advantages and disadvantages in terms of production, cost, and general applications. As a result, monoclonal antibodies are produced only when necessary because their production is a time-consuming and laborious process, although highly rewarding. In this article, the production and application of monoclonal antibodies are illuminated to provide better understanding and formulate new ideas for clinicians and scientists alike.

Kaynakça

  • 1. Selimoğlu SM, Kasap M, Akpınar G, Karadenizli A. Monoklonal Antikor Teknolojisinin Dünü, Bugünü Ve Geleceği. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi. 2016;2(1):6-14.
  • 2. Büyükköroğlu G, Şenel B. Engineering Monoclonal Antibodies. Omics Technologies and Bio-Engineering2018. p. 353-89.
  • 3. Schmidt KV, Wood BA. Trends in cancer therapy: role of monoclonal antibodies. Seminars in Oncology Nursing. 2003;19(3):169-79.
  • 4. İLbasmiŞ Tamer S, DeĞİM İT. Biotechnology Drugs, General Perspective: Review. Turkiye Klinikleri Journal of Pharmacy Sciences. 2016;5(2):77-92.
  • 5. Kaya MM, Tutun H. Monoklonal Antikorlar ve Tedavide Kullanımı. Turkish Journal of Agriculture - Food Science and Technology. 2021;9(3):515-30.
  • 6. Geskin LJ. Monoclonal Antibodies. Dermatologic Clinics. 2015;33(4):777-86.
  • 7. Ansar W, Ghosh S. Monoclonal Antibodies: A Tool in Clinical Research. Indian Journal of Clinical Medicine. 2013;4.
  • 8. Bruno V, Battaglia G, Nicoletti F. The advent of monoclonal antibodies in the treatment of chronic autoimmune diseases. Neurological Sciences. 2010;31(S3):283-8.
  • 9. Suzuki M, Kato C, Kato A. Therapeutic antibodies: their mechanisms of action and the pathological findings they induce in toxicity studies. Journal of Toxicologic Pathology. 2015;28(3):133-9.
  • 10. Wacoo AP, Wendiro D, Vuzi PC, Hawumba JF. Methods for Detection of Aflatoxins in Agricultural Food Crops. Journal of Applied Chemistry. 2014;2014:1-15.
  • 11. Chadseesuwan U, Sangdokmai A, Pimpitak U, Puthong S, Palaga T, Komolpis K. Production of a monoclonal antibody against aflatoxin M1 and its application for detection of aflatoxin M1 in fortified milk. Journal of Food and Drug Analysis. 2016;24(4):780-7.
  • 12. Morel N, Volland H, Dano J, Lamourette P, Sylvestre P, Mock M, et al. Fast and Sensitive Detection of Bacillus anthracis Spores by Immunoassay. Applied and Environmental Microbiology. 2012;78(18):6491-8.
  • 13. Waller D, Hew B, Holdaway C, Jen M, Peckham G. Rapid Detection of Bacillus anthracis Spores Using Immunomagnetic Separation and Amperometry. Biosensors. 2016;6(4).
  • 14. Yang Y. Cancer immunotherapy: harnessing the immune system to battle cancer. Journal of Clinical Investigation. 2015;125(9):3335-7.
  • 15. Li GN, Wang SP, Xue X, Qu XJ, Liu HP. Monoclonal antibody-related drugs for cancer therapy. Drug Discov Ther. 2013;7(5):178-84.
  • 16. Glassman PM, Balthasar JP. Mechanistic considerations for the use of monoclonal antibodies for cancer therapy. Cancer Biol Med. 2014;11(1):20-33.
  • 17. Breedveld FC. Therapeutic monoclonal antibodies. The Lancet. 2000;355(9205):735-40.
  • 18. Wang-Lin S, Balthasar J. Pharmacokinetic and Pharmacodynamic Considerations for the Use of Monoclonal Antibodies in the Treatment of Bacterial Infections. Antibodies. 2018;7(1).
  • 19. Kummerfeldt C. Raxibacumab: potential role in the treatment of inhalational anthrax. Infection and Drug Resistance. 2014.
  • 20. Greig SL. Obiltoxaximab: First Global Approval. Drugs. 2016;76(7):823-30.
  • 21. Matucci A, Nencini F, Pratesi S, Maggi E, Vultaggio A. An overvi
  • 22. Meisel K, Rizvi S. Complications of monoclonal antibody therapy. Med Health R I. 2011;94(11):317-9.
  • 23. Hansel TT, Kropshofer H, Singer T, Mitchell JA, George AJT. The safety and side effects of monoclonal antibodies. Nature Reviews Drug Discovery. 2010;9(4):325-38.
  • 24. Liu HF, Ma J, Winter C, Bayer R. Recovery and purification process development for monoclonal antibody production. MAbs. 2010;2(5):480-99.
  • 25. Nelson PN. Demystified ...: Monoclonal antibodies. Molecular Pathology. 2000;53(3):111-7.
  • 26. KÖHler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256(5517):495-7.
  • 27. Zhang C. Hybridoma Technology for the Generation of Monoclonal Antibodies. Antibody Methods and Protocols. Methods in Molecular Biology2012. p. 117-35.
  • 28. Stacey A. Animal Cell Types, Hybridoma Cells. Encyclopedia of Cell Technology2003.
  • 29. Winzeler A, Wang JT. Culturing Hybridoma Cell Lines for Monoclonal Antibody Production. Cold Spring Harbor Protocols. 2013;2013(7).
  • 30. Zaroff S, Tan G. Hybridoma technology: the preferred method for monoclonal antibody generation for in vivo applications. BioTechniques. 2019;67(3):90-2.
  • 31. Kim H-Y, Stojadinovic A, Izadjoo MJ. Immunization, Hybridoma Generation, and Selection for Monoclonal Antibody Production. Monoclonal Antibodies. Methods in Molecular Biology2014. p. 33-45.
  • 32. Holzlöhner P, Hanack K. Generation of Murine Monoclonal Antibodies by Hybridoma Technology. Journal of Visualized Experiments. 2017(119).
  • 33. Pornnoppadol G, Zhang B, Desai AA, Berardi A, Remmer HA, Tessier PM, et al. A hybridoma-derived monoclonal antibody with high homology to the aberrant myeloma light chain. PLoS One. 2021;16(10):e0252558.
  • 34. Yokoyama WM. Monoclonal antibody supernatant and ascites fluid production. Curr Protoc Immunol. 2001;Chapter 2:Unit 2 6.
  • 35. Smith GP. Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science. 1985;228(4705):1315-7.
  • 36. Parmley SF, Smith GP. Antibody-selectable filamentous fd phage vectors: affinity purification of target genes. Gene. 1988;73(2):305-18.
  • 37. Bird RE, Hardman KD, Jacobson JW, Johnson S, Kaufman BM, Lee SM, et al. Single-chain antigen-binding proteins. Science. 1988;242(4877):423-6.
  • 38. Knappik A, Ge L, Honegger A, Pack P, Fischer M, Wellnhofer G, et al. Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides. J Mol Biol. 2000;296(1):57-86.
  • 39. Soderlind E, Strandberg L, Jirholt P, Kobayashi N, Alexeiva V, Aberg AM, et al. Recombining germline-derived CDR sequences for creating diverse single-framework antibody libraries. Nat Biotechnol. 2000;18(8):852-6.
  • 40. Hoet RM, Cohen EH, Kent RB, Rookey K, Schoonbroodt S, Hogan S, et al. Generation of high-affinity human antibodies by combining donor-derived and synthetic complementarity-determining-region diversity. Nat Biotechnol. 2005;23(3):344-8.
  • 41. Dubel S. Recombinant therapeutic antibodies. Appl Microbiol Biotechnol. 2007;74(4):723-9.
  • 42. Romani C, Cocco E, Bignotti E, Moratto D, Bugatti A, Todeschini P, et al. Evaluation of a novel human IgG1 anti-claudin3 antibody that specifically recognizes its aberrantly localized antigen in ovarian cancer cells and that is suitable for selective drug delivery. Oncotarget. 2015;6(33):34617-28.
  • 43. Schutte M, Thullier P, Pelat T, Wezler X, Rosenstock P, Hinz D, et al. Identification of a putative Crf splice variant and generation of recombinant antibodies for the specific detection of Aspergillus fumigatus. PLoS One. 2009;4(8):e6625.
  • 44. Zhou M, Meyer T, Koch S, Koch J, von Briesen H, Benito JM, et al. Identification of a new epitope for HIV-neutralizing antibodies in the gp41 membrane proximal external region by an Env-tailored phage display library. Eur J Immunol. 2013;43(2):499-509.
  • 45. Lee J, Kim JH, Kim BN, Kim T, Kim S, Cho BK, et al. Identification of novel paraben-binding peptides using phage display. Environ Pollut. 2020;267:115479. 46. Andersen PS, Haahr-Hansen M, Coljee VW, Hinnerfeldt FR, Varming K, Bregenholt S, et al. Extensive restrictions in the VH sequence usage of the human antibody response against the Rhesus D antigen. Mol Immunol. 2007;44(4):412-22.
  • 47. Frandsen TP, Naested H, Rasmussen SK, Hauptig P, Wiberg FC, Rasmussen LK, et al. Consistent manufacturing and quality control of a highly complex recombinant polyclonal antibody product for human therapeutic use. Biotechnol Bioeng. 2011;108(9):2171-81.
  • 48. Robak T, Windyga J, Trelinski J, von Depka Prondzinski M, Giagounidis A, Doyen C, et al. Rozrolimupab, a mixture of 25 recombinant human monoclonal RhD antibodies, in the treatment of primary immune thrombocytopenia. Blood. 2012;120(18):3670-6.
  • 49. Ecker DM, Jones SD, Levine HL. The therapeutic monoclonal antibody market. mAbs. 2015;7(1):9-14. 50. Shukla AA, Wolfe LS, Mostafa SS, Norman C. Evolving trends in mAb production processes. Bioengineering & Translational Medicine. 2017;2(1):58-69.
  • 51. Brantley TJ, Mitchelson FG, Khattak SF. A class of low‐cost alternatives to kifunensine for increasing high mannose N‐linked glycosylation for monoclonal antibody production in Chinese hamster ovary cells. Biotechnology Progress. 2020;37(1).
  • 52. Lu R-M, Hwang Y-C, Liu IJ, Lee C-C, Tsai H-Z, Li H-J, et al. Development of therapeutic antibodies for the treatment of diseases. Journal of Biomedical Science. 2020;27(1).
  • 53. https://www.ncbi.nlm.nih.gov/books/NBK548844/ (16/03/2022, Date of Access)
Yıl 2022, Cilt: 3 Sayı: 1, 298 - 309, 07.04.2022

Öz

Kaynakça

  • 1. Selimoğlu SM, Kasap M, Akpınar G, Karadenizli A. Monoklonal Antikor Teknolojisinin Dünü, Bugünü Ve Geleceği. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi. 2016;2(1):6-14.
  • 2. Büyükköroğlu G, Şenel B. Engineering Monoclonal Antibodies. Omics Technologies and Bio-Engineering2018. p. 353-89.
  • 3. Schmidt KV, Wood BA. Trends in cancer therapy: role of monoclonal antibodies. Seminars in Oncology Nursing. 2003;19(3):169-79.
  • 4. İLbasmiŞ Tamer S, DeĞİM İT. Biotechnology Drugs, General Perspective: Review. Turkiye Klinikleri Journal of Pharmacy Sciences. 2016;5(2):77-92.
  • 5. Kaya MM, Tutun H. Monoklonal Antikorlar ve Tedavide Kullanımı. Turkish Journal of Agriculture - Food Science and Technology. 2021;9(3):515-30.
  • 6. Geskin LJ. Monoclonal Antibodies. Dermatologic Clinics. 2015;33(4):777-86.
  • 7. Ansar W, Ghosh S. Monoclonal Antibodies: A Tool in Clinical Research. Indian Journal of Clinical Medicine. 2013;4.
  • 8. Bruno V, Battaglia G, Nicoletti F. The advent of monoclonal antibodies in the treatment of chronic autoimmune diseases. Neurological Sciences. 2010;31(S3):283-8.
  • 9. Suzuki M, Kato C, Kato A. Therapeutic antibodies: their mechanisms of action and the pathological findings they induce in toxicity studies. Journal of Toxicologic Pathology. 2015;28(3):133-9.
  • 10. Wacoo AP, Wendiro D, Vuzi PC, Hawumba JF. Methods for Detection of Aflatoxins in Agricultural Food Crops. Journal of Applied Chemistry. 2014;2014:1-15.
  • 11. Chadseesuwan U, Sangdokmai A, Pimpitak U, Puthong S, Palaga T, Komolpis K. Production of a monoclonal antibody against aflatoxin M1 and its application for detection of aflatoxin M1 in fortified milk. Journal of Food and Drug Analysis. 2016;24(4):780-7.
  • 12. Morel N, Volland H, Dano J, Lamourette P, Sylvestre P, Mock M, et al. Fast and Sensitive Detection of Bacillus anthracis Spores by Immunoassay. Applied and Environmental Microbiology. 2012;78(18):6491-8.
  • 13. Waller D, Hew B, Holdaway C, Jen M, Peckham G. Rapid Detection of Bacillus anthracis Spores Using Immunomagnetic Separation and Amperometry. Biosensors. 2016;6(4).
  • 14. Yang Y. Cancer immunotherapy: harnessing the immune system to battle cancer. Journal of Clinical Investigation. 2015;125(9):3335-7.
  • 15. Li GN, Wang SP, Xue X, Qu XJ, Liu HP. Monoclonal antibody-related drugs for cancer therapy. Drug Discov Ther. 2013;7(5):178-84.
  • 16. Glassman PM, Balthasar JP. Mechanistic considerations for the use of monoclonal antibodies for cancer therapy. Cancer Biol Med. 2014;11(1):20-33.
  • 17. Breedveld FC. Therapeutic monoclonal antibodies. The Lancet. 2000;355(9205):735-40.
  • 18. Wang-Lin S, Balthasar J. Pharmacokinetic and Pharmacodynamic Considerations for the Use of Monoclonal Antibodies in the Treatment of Bacterial Infections. Antibodies. 2018;7(1).
  • 19. Kummerfeldt C. Raxibacumab: potential role in the treatment of inhalational anthrax. Infection and Drug Resistance. 2014.
  • 20. Greig SL. Obiltoxaximab: First Global Approval. Drugs. 2016;76(7):823-30.
  • 21. Matucci A, Nencini F, Pratesi S, Maggi E, Vultaggio A. An overvi
  • 22. Meisel K, Rizvi S. Complications of monoclonal antibody therapy. Med Health R I. 2011;94(11):317-9.
  • 23. Hansel TT, Kropshofer H, Singer T, Mitchell JA, George AJT. The safety and side effects of monoclonal antibodies. Nature Reviews Drug Discovery. 2010;9(4):325-38.
  • 24. Liu HF, Ma J, Winter C, Bayer R. Recovery and purification process development for monoclonal antibody production. MAbs. 2010;2(5):480-99.
  • 25. Nelson PN. Demystified ...: Monoclonal antibodies. Molecular Pathology. 2000;53(3):111-7.
  • 26. KÖHler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256(5517):495-7.
  • 27. Zhang C. Hybridoma Technology for the Generation of Monoclonal Antibodies. Antibody Methods and Protocols. Methods in Molecular Biology2012. p. 117-35.
  • 28. Stacey A. Animal Cell Types, Hybridoma Cells. Encyclopedia of Cell Technology2003.
  • 29. Winzeler A, Wang JT. Culturing Hybridoma Cell Lines for Monoclonal Antibody Production. Cold Spring Harbor Protocols. 2013;2013(7).
  • 30. Zaroff S, Tan G. Hybridoma technology: the preferred method for monoclonal antibody generation for in vivo applications. BioTechniques. 2019;67(3):90-2.
  • 31. Kim H-Y, Stojadinovic A, Izadjoo MJ. Immunization, Hybridoma Generation, and Selection for Monoclonal Antibody Production. Monoclonal Antibodies. Methods in Molecular Biology2014. p. 33-45.
  • 32. Holzlöhner P, Hanack K. Generation of Murine Monoclonal Antibodies by Hybridoma Technology. Journal of Visualized Experiments. 2017(119).
  • 33. Pornnoppadol G, Zhang B, Desai AA, Berardi A, Remmer HA, Tessier PM, et al. A hybridoma-derived monoclonal antibody with high homology to the aberrant myeloma light chain. PLoS One. 2021;16(10):e0252558.
  • 34. Yokoyama WM. Monoclonal antibody supernatant and ascites fluid production. Curr Protoc Immunol. 2001;Chapter 2:Unit 2 6.
  • 35. Smith GP. Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science. 1985;228(4705):1315-7.
  • 36. Parmley SF, Smith GP. Antibody-selectable filamentous fd phage vectors: affinity purification of target genes. Gene. 1988;73(2):305-18.
  • 37. Bird RE, Hardman KD, Jacobson JW, Johnson S, Kaufman BM, Lee SM, et al. Single-chain antigen-binding proteins. Science. 1988;242(4877):423-6.
  • 38. Knappik A, Ge L, Honegger A, Pack P, Fischer M, Wellnhofer G, et al. Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides. J Mol Biol. 2000;296(1):57-86.
  • 39. Soderlind E, Strandberg L, Jirholt P, Kobayashi N, Alexeiva V, Aberg AM, et al. Recombining germline-derived CDR sequences for creating diverse single-framework antibody libraries. Nat Biotechnol. 2000;18(8):852-6.
  • 40. Hoet RM, Cohen EH, Kent RB, Rookey K, Schoonbroodt S, Hogan S, et al. Generation of high-affinity human antibodies by combining donor-derived and synthetic complementarity-determining-region diversity. Nat Biotechnol. 2005;23(3):344-8.
  • 41. Dubel S. Recombinant therapeutic antibodies. Appl Microbiol Biotechnol. 2007;74(4):723-9.
  • 42. Romani C, Cocco E, Bignotti E, Moratto D, Bugatti A, Todeschini P, et al. Evaluation of a novel human IgG1 anti-claudin3 antibody that specifically recognizes its aberrantly localized antigen in ovarian cancer cells and that is suitable for selective drug delivery. Oncotarget. 2015;6(33):34617-28.
  • 43. Schutte M, Thullier P, Pelat T, Wezler X, Rosenstock P, Hinz D, et al. Identification of a putative Crf splice variant and generation of recombinant antibodies for the specific detection of Aspergillus fumigatus. PLoS One. 2009;4(8):e6625.
  • 44. Zhou M, Meyer T, Koch S, Koch J, von Briesen H, Benito JM, et al. Identification of a new epitope for HIV-neutralizing antibodies in the gp41 membrane proximal external region by an Env-tailored phage display library. Eur J Immunol. 2013;43(2):499-509.
  • 45. Lee J, Kim JH, Kim BN, Kim T, Kim S, Cho BK, et al. Identification of novel paraben-binding peptides using phage display. Environ Pollut. 2020;267:115479. 46. Andersen PS, Haahr-Hansen M, Coljee VW, Hinnerfeldt FR, Varming K, Bregenholt S, et al. Extensive restrictions in the VH sequence usage of the human antibody response against the Rhesus D antigen. Mol Immunol. 2007;44(4):412-22.
  • 47. Frandsen TP, Naested H, Rasmussen SK, Hauptig P, Wiberg FC, Rasmussen LK, et al. Consistent manufacturing and quality control of a highly complex recombinant polyclonal antibody product for human therapeutic use. Biotechnol Bioeng. 2011;108(9):2171-81.
  • 48. Robak T, Windyga J, Trelinski J, von Depka Prondzinski M, Giagounidis A, Doyen C, et al. Rozrolimupab, a mixture of 25 recombinant human monoclonal RhD antibodies, in the treatment of primary immune thrombocytopenia. Blood. 2012;120(18):3670-6.
  • 49. Ecker DM, Jones SD, Levine HL. The therapeutic monoclonal antibody market. mAbs. 2015;7(1):9-14. 50. Shukla AA, Wolfe LS, Mostafa SS, Norman C. Evolving trends in mAb production processes. Bioengineering & Translational Medicine. 2017;2(1):58-69.
  • 51. Brantley TJ, Mitchelson FG, Khattak SF. A class of low‐cost alternatives to kifunensine for increasing high mannose N‐linked glycosylation for monoclonal antibody production in Chinese hamster ovary cells. Biotechnology Progress. 2020;37(1).
  • 52. Lu R-M, Hwang Y-C, Liu IJ, Lee C-C, Tsai H-Z, Li H-J, et al. Development of therapeutic antibodies for the treatment of diseases. Journal of Biomedical Science. 2020;27(1).
  • 53. https://www.ncbi.nlm.nih.gov/books/NBK548844/ (16/03/2022, Date of Access)
Toplam 51 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Klinik Tıp Bilimleri
Bölüm Derlemeler
Yazarlar

Hamit Yıldız 0000-0001-7858-5123

Mehmet Tahir Hüsunet 0000-0003-1424-5132

İbrahim Halil Kenger

Erken Görünüm Tarihi 31 Mart 2022
Yayımlanma Tarihi 7 Nisan 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 3 Sayı: 1

Kaynak Göster

Vancouver Yıldız H, Hüsunet MT, Kenger İH. Monoclonal Antibodies: Production, Techniques, and Global Marketing. Exp Appl Med Sci. 2022;3(1):298-309.

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