Human Monoclonal Antibody Technology

  • K. James
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 113)

Abstract

The success of Kohler and Milstein (1975) in immortalizing specific antibody secreting cell lines of rodent origin inevitably led to similar attempts to generate human monoclonals. Initially this effort was largely driven by the belief that such products would be clinically (especially therapeutically) superior to their rodent counterparts. In addition to being less immunogenic than rodent antibodies it was also felt that they might recognize more appropriate target antigens and be more efficient at triggering complement and antibody dependent cellular cytotoxic actions in vivo as indeed has proved to be the case. Further impetus was given by the difficulties experienced in producing useful rodent monoclonals against a number of targets of clinical interest including RhD, histocompatability and tumour antigens. This was attributable to the failure of the rodent immune system to recognize the relevant epitopes against a background of immunodominant epitopes. However additional interest in human monoclonal antibody technology has come from an increasing awareness of its potential for investigating the human humoral immune system (e.g., James 1989).

Keywords

SCID Mouse Human Monoclonal Antibody Human Peripheral Blood Lymphocyte Variable Region Gene Cell Surface Phenotype 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aulitsky WE, Schulz TF, Tilg H, Niederwieser D, Larcher K, Östberg L, Scriba M, Martindale J, Stern AC, Grass P, Mach M, Dierich MP, Huber C (1991) Human monoclonal antibodies neutralizing cytomegalovirus (CMV) for prophylaxis of CMV disease: report of a phase 1 trial in bone marrow transplant recipients. J Infect Dis 163:1344–1347CrossRefGoogle Scholar
  2. Banchereau J, De Paoli P, Vallé A, Garcia E, Rousset F (1991) Long term human B cell lines dependent on interleukin-4 and antibody to CD40. Science 25:70–72CrossRefGoogle Scholar
  3. Borrebaeck CAK (1988a) Critical appraisal of the in vitro immunization technology for the production of mouse and human monoclonal antibodies. Adv Drug Rev 2:143–165CrossRefGoogle Scholar
  4. Borrebaeck CAK (ed) (1988b) In vitro immunization in hybridoma technology. Prog Biotechnol 5Google Scholar
  5. Brams P, Royston I, Boerner P (1992) Induction of secondary responses following induction of primary responses on human spleen cells by in vitro immunisation. Presented at the 2nd international conference on human antibodies and hybridomas. Cambridge, England, March 1992Google Scholar
  6. Boyd JE, James K (1989) Human monoclonal antibodies: their potential, problems and prospects. Adv Biotechnol Proc 11:1–43Google Scholar
  7. Boyd JE, James K (1992) B cell responses to HIV and the development of human monoclonal antibodies. Clin Exp Immunol 88:189–202PubMedCrossRefGoogle Scholar
  8. Brown CMS, Longhurst C, Haynes C, Plater-Zyberk C, Malcolm A, Maini RN (1992) Immunoglobulin heavy chain variable region gene utilization by B cell hybridomas derived from rheumatoid synovial tissue. Clin Exp Immunol 89:230–238PubMedCrossRefGoogle Scholar
  9. Burton DR (1991) Human and mouse monoclonal antibodies by repertoire cloning. TIBTECH 9:169–175CrossRefGoogle Scholar
  10. Cairns E, Kwong PC, Misener V, Ip P, Bell DA, Siminovitch KA (1989) Analysis of variable region genes encoding a human anti-DNA antibody of normal origin. Implications for the molecular basis of human autoimmune responses. J Immunol 143:685–691PubMedGoogle Scholar
  11. Carlsson R, Mårtensson C, Kalliomäki S, Ohlin M, Borrebaeck CAK (1992) Human peripheral blood lymphocytes transplanted into SCID mice constitute an in vivo culture system exhibiting several parameters found in a normal immune response and are a source of immunocytes for the production of human monoclonal antibodies. J Immunol 148:1065–1071PubMedGoogle Scholar
  12. Carson DE, Freimark BD (1986) Human lymphocyte hybridomas and monoclonal antibodies. Adv Immunol 38:275–311PubMedCrossRefGoogle Scholar
  13. Chiswell DJ, McCafferty J (1992) Phage antibodies: will new “coliclonal” antibodies replace monoclonal antibodies. TIBTECH 10:80–84CrossRefGoogle Scholar
  14. Ditzel H, Erb K, Borup-Christensen P, Neilsen B, Jensenius JC (1991) Evaluation of procedures for the fixation and processing of human tissue for immunohisto-chemical analysis of human monoclonal antibodies. Human Antibod Hybird 2:135–141Google Scholar
  15. Drobyski WR, Gottlieb M, Carrigan D, Ostberg L, Grebenau M, Schran H, Magid P, Ehrlich P, Nadler PI, Ash RC (1991) Phase 1 study of safety and pharmacokinetics of a human anticytomegalovirus monoclonal antibody in allogeneic bone marrow transplant recipients. Transplantation 51:1190–1196PubMedCrossRefGoogle Scholar
  16. Duchosal MA, Sabine AE, Fischer P, Leturcq D, Barbas CF, McConahey PJ, Caothien RH, Thornton GB, Dixon FJ, Burton DR (1992) Immunization of hu-PBL-SCID mice and the rescue of human monoclonal Fab fragments through combinatorial libraries. Nature 355:258–262PubMedCrossRefGoogle Scholar
  17. Engelman EG, Found SKH, Larrick J, Raubitschek A (1985) Human hybridomas and monoclonal antibodies. Plenum, New YorkGoogle Scholar
  18. Folks TM (1987) Epitope mapping of human immunodeficiency virus: a monoclonal approach. J Immunol 139:3913–3914PubMedGoogle Scholar
  19. Foung SKH, Perkins S (1989) Electric field induced cell fusion and human monoclonal antibodies. J Immunol Methods 116:117–122PubMedCrossRefGoogle Scholar
  20. Foung S, Perkins S, Kafader K, Gessner P, Zimmerman U (1990) Development of microfusion techniques to generate human hybridomas. J Immunol Methods 134:35–42PubMedCrossRefGoogle Scholar
  21. Frasa H, Torensma R, Verhoef J (1992) A human IgM monoclonal antibody against human TNF. Presented at the 2nd internation conference on: human antibodies and hybridomas. Cambridge, EnglandGoogle Scholar
  22. Gillies SD, Dorai H, Wesolowski J, Majeau G, Young D, Boyd J, Gardner J, James K (1989) Expression of human antitetanus antibody in transfected murine myeloma cells. Biotechnology 7:799–804CrossRefGoogle Scholar
  23. James K (1989) Human monoclonal antibody technology — are its achievements, challenges and potential appreciated. Scand J Immunol 29:257–264PubMedCrossRefGoogle Scholar
  24. James K (1990a) Therapeutic monoclonal antibodies — their production and application. Animal Cell Biotechnol 4:206–255Google Scholar
  25. James K (1990b) Human monoclonal antibodies and engineered antibodies in the management of cancer. Semin Cancer Biol 1:243–253PubMedGoogle Scholar
  26. James K, Bell GT (1987) Human monoclonal antibody production. Current status and future prospects. J Immunol Methods 100:5–40PubMedCrossRefGoogle Scholar
  27. James K, Gardner J, Skibinski G, McCann M, Thorpe R, Gearing A, Gordon J (1990) Cell surface phenotype, cytokines, and antibody gene expression in immortalized human B cell lines. Human Antibod Hybrid 1:145–153Google Scholar
  28. Jung G, Freimann U, von Marschall Z, Reisfeld RA, Wilmans W (1991) Target cell-induced T cell activation with bi and trispecific antibody fragments. Eur J Immunol 21:2431–2435PubMedCrossRefGoogle Scholar
  29. Köhler G, Milstein C (1975) Continuous culture of fused cells secreting antibody of predefined specificity. Nature 256:495–497PubMedCrossRefGoogle Scholar
  30. Komori S, Yamasaki N, Shigeta M, Isojima S, Watanabe T (1988) Production of heavy chain class-switch variants of human monoclonal antibody by recombinant DNA Technology. Clin Exp Immunol 71:508–516PubMedGoogle Scholar
  31. Kosinski S, Hämmerling (1986) A new cloning method for antibody-forming lym-phoblastoid cells. Increase in cloning efficiency by inclusion of human fibroblasts into semisolid agarose growth layer. J Immunol Methods 94:201–208PubMedCrossRefGoogle Scholar
  32. Kozbor D, Lagarde AE, Roder JC (1982) Human hybridomas constructed with antigen-specific Epstein virus — transformed cell lines. Proc Natl Acad Sci USA 79:6651–6655PubMedCrossRefGoogle Scholar
  33. Larrick JW, Fry KE (1991) Recombinant antibodies. Human Antib Hybrid 2:172–189Google Scholar
  34. Leader KA, Macht LM, Steers F, Kumpel BM, Elson CJ (1992) Antibody responses to the blood group antigen D in SCID mice reconstituted with human blood mononuclear cells. Immunology 76:222–234Google Scholar
  35. Lewis AP, Parry N, Peakman TC, Scott Crowe J (1992) Rescue and expression of human immunoglobulin genes to generate functional human monoclonal antibodies. Human Antib Hybrid 3:146–152Google Scholar
  36. Masuho Y (1988) Human monoclonal antibodies: prospects for use as passive immunotherapy. Serodiag Immunother Infect Dis 2:319–340CrossRefGoogle Scholar
  37. McCann MC, James K, Kumpel BM (1988) Production and use of human monoclonal anti-D antibodies. J Immunol Methods 115:3–15PubMedCrossRefGoogle Scholar
  38. Nakatani T, Nomura N, Horigome K, Ohtsuka H, Noguchi H (1989) Functional expression of human monoclonal antibody genes directed against pseudomonal exotoxin A in mouse myeloma cells. Biotechnology 7:805–900CrossRefGoogle Scholar
  39. Pistillo MP, Mazzoleni O, Tanigaki N, Hammerling U, Longo A, Frumento G, Ferrara GB (1988) Human anti-HLA monoclonal antibodies: production, characterization and application. Hum Immunol 21:265–278PubMedCrossRefGoogle Scholar
  40. Sanz I, Casali P, Thomas JW, Notkins AL, Capra JD (1989) Nucleotide sequences of eight human natural autoantibody VH regions reveals apparent restricted use of VH families. J Immunol 142:4054–4061PubMedGoogle Scholar
  41. Shinmoto H, Dosakao S, Tachibana H, Yamada K, Sanetaka S, Murakami H (1991) Generation of hybrid hybridomas secreting human IgM class hybrid antiricin and antidiptheria toxin antibodies. Human Antibod Hybrid 2:39–41Google Scholar
  42. Steenbakkers PGA, van Meel FCM, Olijve W (1992) A new approach to the generation of human and murine antibody producing hybridomas. J Immunol Methods 152:69–77PubMedCrossRefGoogle Scholar
  43. Strelkauskas AJ (ed) (1987) Human hybridomas. Dekker, New YorkGoogle Scholar
  44. Thompson KM, Randen I, Natvig JB, Mageed RA, Jefferis R, Carson DA, Tighe H, Forre O (1990) Human monoclonal rheumatoid factors derived from the polyclonal repertoire of rheumatoid synovial tissue: incidence of cross-reactive idiotopes and expression of VH and VK subgroups. Eur J Immunol 20:863–868PubMedCrossRefGoogle Scholar
  45. Thompson KM, Sutherland J, Barden G, Melamed MD, Wright MG, Bailey S, Thorpe SJ (1992) Human monoclonal antibodies specific for blood group antigens demonstrate multispecific properties characteristic of natural autoantibodies. Immunology 76:146–157PubMedGoogle Scholar
  46. Tutt A, Stevenson GT, Glennie MT (1991) Trispecific F(ab′)3 derivatives that use cooperative signalling via the TCR/CD3 complex and CD2 to activate and redirect resting cytotoxic T cells. J Immunol 147:60–69PubMedGoogle Scholar
  47. Williams SS, Umemoto T, Kida H, Repasky EA, Bankert RB (1992) Engraftment of human peripheral blood leukocytes into severe combined immunodeficient mice results in the longterm and dynamic production of human xenoreactive antibodies. J Immunol 149:2830–2836PubMedGoogle Scholar
  48. Winter G, Milstein C (1991) Man-made antibodies. Nature 349:293–299PubMedCrossRefGoogle Scholar
  49. Wolff EA, Esselstyn J, Maloney G, Raff HV (1992) Human monoclonal antibody homodimers. Effect of valency on in vitro and in vivo antibacterial activity. J Immunol 148:2469–2474PubMedGoogle Scholar
  50. Ziegler EJ, Fisher CJ, Sprung CL, Straube RC, Sadoff JC, Foulke GE, Wortel CH, Fink MP, Dellinger RP, Teng NNH, Allen IE, Berger HJ, Knatterud GL, LoBuglio AF, Smith CR and the HA-1 A Sepsis Study Group (1991) Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double blind, placebo-controlled trial. N Engl J Med 324:429–436PubMedCrossRefGoogle Scholar
  51. Zimmermann U, Vienken J (1982) Electric field induced cell to cell fusion. J Membr Biol 67:165–182PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1994

Authors and Affiliations

  • K. James

There are no affiliations available

Personalised recommendations