Molecular and Cellular Biochemistry

, Volume 62, Issue 2, pp 109–120 | Cite as

Human monoclonal antibodies

  • S. P. C. Cole
  • B. G. Campling
  • T. Atlaw
  • D. Kozbor
  • J. C. Roder
Current Thinking


The technology for the production of murine monoclonal antibodies has been refined enormously since its introduction in 1975. However, the technology for generating human monoclonal antibodies has only recently come into its own. In this review, three currently available approaches to the production of human monoclonal antibodies are described. These include the hybridoma technique, based on the fusion of antibody-producing human B lymphocytes with either mouse or human myeloma or lymphoblastoid cells; the EBV immortalization technique, based on the use of Epstein-Barr virus (EBV) to ‘immortalize’ antigen-specific human B lymphocytes; and the EBV-hybridoma technique, based on a combination of the first two methods.

The EBV-hybridoma system retains the advantageous features of the other two systems while overcoming their pitfalls and may be the current method of choice for producing human monoclonal antibodies with a defined specificity.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kohler G and Milstein C. Nature 256:495–497, 1975.PubMedGoogle Scholar
  2. 2.
    Steplewski Z (editor). Hybridoma (Vol 1, 1982).Google Scholar
  3. 3.
    Levy RL and Miller RA. Ann Rev Med 34:107–116, 1983.Google Scholar
  4. 4.
    Miller RA and Levy R. Lancet 2:226–230, 1981.Google Scholar
  5. 5.
    Miller RA, Maloney DG, Warnke R and Levy R. N Engl J Med 306:517–522, 1982.Google Scholar
  6. 6.
    Miller RA, Maloney DG, McKillop J and Levy R. Blood 58:78–86, 1981.Google Scholar
  7. 7.
    Ritz J, Pesando JM, Sallan SE, Clavell LA, Notis-McConarty J, Rosenthal P and Schlossman SF. Blood 58:141–151, 1981.Google Scholar
  8. 8.
    Sears HF, Atkinson B, Herlyn D, Ernst C, Matteis J, Steplewski Z and Koprowski H. Lancet 1:762–765, 1982.Google Scholar
  9. 9.
    Nadler LM, Stashenko P, Hardy R, Kaplan WD, Button LN, Kufe DW, Amman KH and Schlossman SF. Cancer Res 40:3147–3154, 1980.Google Scholar
  10. 10.
    Dillman RO, Shawler DL, Sobol RE, Collins HA, Beauregard JC, Wormsley SB and Royston I. Blood 59:1036–1045, 1982.Google Scholar
  11. 11.
    Roder JC, Bell DA and Singhal SK. J Immunol 121:29–37, 1978.Google Scholar
  12. 12.
    Hammarström LE, Smith E, Primi D and Moller G. Nature 263:60–61, 1976.Google Scholar
  13. 13.
    Fugi H and Milgrom F. J Exp Med 138:16–32, 1973.Google Scholar
  14. 14.
    Langone JJ and Van Vunakis H (eds). Meth Enzymol 92: Pt. E., 1983.Google Scholar
  15. 15.
    Kozbor D, Dexter D and Roder JC. Hybridoma 2:7–16, 1983.Google Scholar
  16. 16.
    Schwaber J. Exp Cell Res 93:343–354, 1975.Google Scholar
  17. 17.
    Levy R and Dilley J. Proc Natl Acad Sci USA 75:2411–2415, 1978.Google Scholar
  18. 18.
    Levy R, Dilley J, Brown S and Bergman Y. In: Monoclonal Antibodies. Hybridomas: A New Dimension in Biological Analysis (Kennett RH, McKearn TJ and Bechtol KB, eds), pp 137–153, Plenum Press, New York, 1980.Google Scholar
  19. 19.
    Kennett RH. Meth Enzymol 58:345–359, 1979.Google Scholar
  20. 20.
    Croce CM, Shander M, Martinis J, Circurel L, D'Ancoma, GG, Dolby TW and Koprowski H. Proc Natl Acad Sci USA 76:3416–3419, 1979.Google Scholar
  21. 21.
    Erikson J, Martinis J and Croce CM. Nature 294:173–175, 1981.Google Scholar
  22. 22.
    Kozbor D, Roder JC, Chang TH, Steplewski Z and Koprowski H. Hybridoma 1:323–328, 1982.Google Scholar
  23. 23.
    Nowinski R, Berglund C, Lane J, Lostrom M, Bernstein J, Young W and Hakomori S. Science 210:537–539, 1980.Google Scholar
  24. 24.
    Lane HC, Shelhamer JH, Mostowski HS and Fauci AS. J Exp Med 155:333–337, 1982.Google Scholar
  25. 25.
    Gigliotti F and Insel RA. J Clin Invest 70:1306–1309, 1982.Google Scholar
  26. 26.
    Butler, JL, Lane HC and Fauci AS. J Immunol 130:165–168, 1983.Google Scholar
  27. 27.
    Sikora K and Wright R. Br J Cancer 43:696–700, 1981.Google Scholar
  28. 28.
    Sikora K and Phillips J. Br J Cancer 43:105–107, 1981.Google Scholar
  29. 29.
    Schlom J, Wunderlich D and Teramoto YA. Proc Natl Acad. Sci USA 77:6841–6845, 1980.Google Scholar
  30. 30.
    Satoh J, Prabhakar BS, Haspel MV, Ginsberg-Fellner F and Notkins AL. N Engl J Med 309:217–220, 1983.Google Scholar
  31. 31.
    Croce CM, Shander M, Martinis J, Circurel L, D'Ancoma GG and Koprowski H. Eur J Immunol 10:486–488, 1980.Google Scholar
  32. 32.
    Raison RL, Walker KZ, Halnan CRE, Briscoe D and Basten A. J Exp Med 156:1380–1389, 1980.Google Scholar
  33. 33.
    Matsuoka Y, Moore GE, Yagi Y and Pressman D, 1967. Proc Soc Exp Biol Med 125:1246–1250, 1967Google Scholar
  34. 34.
    Abrams PG, Knost JA, Clarke G, Wilburn S, Oldham RK and Foon KA. J Immunol 131:1201–1204, 1983.Google Scholar
  35. 35.
    Nilsson K, Bennich H, Johansson SGO and Ponten J. Clin Exp Immunol 7:477–489, 1970.Google Scholar
  36. 36.
    Olsson L and Kaplan HS. Proc Natl Acad Sci USA 77:5429–5431, 1980.Google Scholar
  37. 37.
    Teng NNH, Lam KS, Riera FC and Kaplan HS. Proc Natl Acad Sci USA 80:7308–7312, 1983.Google Scholar
  38. 38.
    Togawa A, Nobusama I, Miyamoto K, Hyodo H and Namba M. Int J Cancer 29:495–500, 1982.Google Scholar
  39. 39.
    Karpas A, Fischer P and Swirsky D. Lancet 1:931–933, 1982.Google Scholar
  40. 40.
    Jobin ME, Fahey JL and Price Z. J Exp Med 140:494–507, 1974.Google Scholar
  41. 41.
    Diehl V, Schaadt M, Kirchner H, Hellriegel KP, Gudat F, Fonatsch C, Lskewitz E and Guggenheim R. Blut 36:331–338, 1978.Google Scholar
  42. 42.
    Shustik C, Bergsagel DE and Pruzanski W. Blood 48:41–51, 1976.Google Scholar
  43. 43.
    Burk KH, Drewinko B, Trejillo JM and Ahearn MJ. Cancer Res 38:2508–2511, 1978.Google Scholar
  44. 44.
    Edwards PAW, Smith CM, Neville AM and O'Hare MJ. Eur J Immunol 12:641–648, 1982.Google Scholar
  45. 45.
    Rills RE Jr, Ruiz-Arguelles A, Weyl KG, Bradley AL, Weihmeir B, Jacobsen DJ and Strehlo BL. Int J Cancer 31:133–141, 1983.Google Scholar
  46. 46.
    Sikora K, Alderson T, Ellis J, Phillips J and Watson J. Br J Cancer 47:135–145, 1983.Google Scholar
  47. 47.
    Croce CM, Linnenback A, Hall W, Steplewski Z and Koprowski H. Nature 288:488–491, 1980.Google Scholar
  48. 48.
    Shoenfeld Y, Hsu-Lin SC, Gabriels JE, Silberstein LE, Furie BC, Furie B, Stellar BD and Schwartz RS. J Clin Invest 70:205–208, 1982.Google Scholar
  49. 49.
    Dwyer DS, Bradley RJ, Urguhart CK and Kearney JF. Nature 301:611–614, 1983.Google Scholar
  50. 50.
    Levy JA, Viroloinen V and Defendi V. Cancer 22:517–524, 1968.Google Scholar
  51. 51.
    Glassy MC, Handley HH, Hagiwara H and Royston I. Proc Natl Acad Sci USA 80:6327–6331, 1983.Google Scholar
  52. 52.
    Buck DW, Larrick JW, Raubitschek A, Truitt K, Senyk G, Wang J and Dyer BJ. In: Hybridomas: A New Dimension in Biological Analyses (Kennett, RH, McKearn TJ and Bechtol KB, eds), (in press). Plenum Press, New York.Google Scholar
  53. 53.
    Larrick JW, Truitt KE, Raubitschek AA, Senyk G and Wang JCN. Proc Natl Acad Sci USA 80:6376–6380, 1983.Google Scholar
  54. 54.
    Chiorrazzi N, Wasserman RL and Kunkel HG. J Exp Med 156:930–935, 1982.Google Scholar
  55. 55.
    Sato K, Slesinski RS and Littlefield JW. Proc Natl Acad Sci USA 69:1244–1248, 1972.Google Scholar
  56. 56.
    Lewin R. Science 212:767–769, 1981.Google Scholar
  57. 57.
    Olsson L, Kronstrøm H, Cambon-De Mouzon A, Honsik C, Brodin T and Jakobsen B. J Immunol Meth 61:17–32, 1983.Google Scholar
  58. 58.
    Pickering JW and Gelder FB. J Immunol 129:406–412, 1982.Google Scholar
  59. 59.
    Zeijlemaker WP, Astaldi GCB, Janssen MC, Stricker EAM and Tiebout RE. 15th International Leucocyte Culture Conference, Asilomar, pp 368–369, 1982.Google Scholar
  60. 60.
    Yokochi T, Holly RD and Clark EA. J Immunol 128:823–827, 1982.Google Scholar
  61. 61.
    Eisenbarth GS, Linnenbach A, Jackson R, Scearce R and Croce CM. Nature 300:264–267, 1982.Google Scholar
  62. 62.
    Shoenfeld Y, Rauch J, Massicotte H, Datta SK, Andre-Schwartz J, Stollar BD and Schwartz RS. N Engl J Med 308:414–420, 1983.Google Scholar
  63. 63.
    Sikora K, Alderson T, Phillips J and Watson JV. Lancet 1:11–14, 1982.Google Scholar
  64. 64.
    Phillips J, Sikora K and Watson JV. Lancet 2:1214–1215, 1982.Google Scholar
  65. 65.
    Warenius HM, Taylor JW, Durack BE and Cross PA. Eur J Cancer Clin Oncol 19:347–355, 1983.Google Scholar
  66. 66.
    Brodin T, Olsson L and Sjogren H-O. J Immunol Meth 60:1–7, 1983.Google Scholar
  67. 67.
    Stähl C, Staehelin T, Miggiano V, Schmidt J and Haring P. J Immunol Meth 32:297–304, 1980.Google Scholar
  68. 68.
    68. Kozbor D and Roder JC. Eur J Immunol (in press), 1983.Google Scholar
  69. 69.
    Olsson L and Kaplan HS. Meth Enzymol 92 (Pt E):3–16, 1983.Google Scholar
  70. 70.
    Kozbor D, Lagarde AE and Roder JC. Proc Natl Acad Sci USA 79:6651–6655, 1982.Google Scholar
  71. 71.
    Atlaw T. M.Sc. thesis. Department of Microbiology and Immunology, Queen's University at Kingston, Ontario, Canada, 1983.Google Scholar
  72. 72.
    Southern PJ and Berg P. J Mol Appl Genet 1:322–341, 1982.Google Scholar
  73. 73.
    Kearney JF, Radbrusch A, Liesegang B and Rajewski K. Eur J Immunol 6:292–295, 1976.Google Scholar
  74. 74.
    Kozbor D, and Roder JC. J Immunol 127:1275–1280, 1981.Google Scholar
  75. 75.
    Epstein MA, Achong BG and Barr YM. Lancet 1:702–703, 1964.Google Scholar
  76. 76.
    Epstein MA, Henle G, Achong BG and Barr YM. J Exp Med 121:761–769, 1965.Google Scholar
  77. 77.
    Henle G and Henle W. Trans NY Acad Sci 29:71–79, 1966.Google Scholar
  78. 78.
    Yamaguchi J, Hinuma Y and Grace JT. J Virol 1:640–642, 1967.Google Scholar
  79. 79.
    Henle G, Henle W and Diehl V. Proc Natl Acad Sci USA 59:94–107, 1968.Google Scholar
  80. 80.
    Henle G and Henle W. In: The Epstein-Barr Virus (Epstein MA and Achong BG, eds), pp 297–320, Springer-Verlag, Berlin, 1979.Google Scholar
  81. 81.
    Fialkow PJ, Klein G, Gartler SM and Clifford P. Lancet 1:384–386, 1970.Google Scholar
  82. 82.
    Henderson A, Ripley S, Heller M and Kieff E. Proc Natl Acad Sci USA 80:1987–1991, 1983.Google Scholar
  83. 83.
    Thestrup-Pederson K, Esmann V, Bisballe S, Jensen JR, Pallesen G, Hastrup J, Madsen M, Thorling K, Grazia-Masucci M, Saemundsen AR and Ernberg I. Lancet 2:997–1002, 1980.Google Scholar
  84. 84.
    Epstein MA and Achong BG. In: The Epstein-Barr Virus (Epstein, MA and Achong BC, eds), pp 23–38, Springer-Verlag Berlin, 1979.Google Scholar
  85. 85.
    Bird AG and Britton S. Sem Hematol 19:285–300, 1982.Google Scholar
  86. 86.
    Nonoyama M, Huang CH, Pagano JS, Klein G and Singh S. Proc Natl Acad Sci USA 70:3265–3268, 1973.Google Scholar
  87. 87.
    Henle W, Henle G, Burtin P, Chachin Y, Clifford P, DeSchryver A, De-The G, Diehl V, Ho CH and Klein G. J Nat Cancer Inst 44:225–231, 1970.Google Scholar
  88. 88.
    Klein G. In: The Epstein-Barr Virus (Epstein MA and Achong BG, eds), pp 339–350, Springer-Verlag, Berlin 1979.Google Scholar
  89. 89.
    Wollheim FA and Williams RC. N Engl J Med 274:61–67, 1966.Google Scholar
  90. 90.
    Rosén A, Britton S, Gergely P, Jondal M and Klein G. Nature 267:52–54, 1977.Google Scholar
  91. 91.
    Bird AG and Britton S. Immunol Rev 45:41–67, 1979.Google Scholar
  92. 92.
    Jondal M, Klein G, Oldstone MBA, Bokish V and Yefenof E. Scand J Immunol 5:401–410, 1976.Google Scholar
  93. 93.
    Yefenof E and Klein G. Int J Cancer 20:347–352, 1977.Google Scholar
  94. 94.
    Jondal, M and Klein G. J Exp Med 138:1365–1378, 1973.Google Scholar
  95. 95.
    Greaves ME, Brown G and Rickinson AB. Clin Immunol Immunopathol 3:513–525, 1975.Google Scholar
  96. 96.
    Hansson M, Falk K and Ernberg I. J Exp Med 158:616–622, 1983.Google Scholar
  97. 97.
    Wells A, Godal T, Kvaløy S, Steen HB and Klein G. Differentiation 22:113, 1982.Google Scholar
  98. 98.
    Fu SM, Hurley JN, McCune JM, Kunkel HG and Good RA. J Exp Med 152:1519–1526, 1980.Google Scholar
  99. 99.
    Brown NA and Miller G. J Immunol 128:24–29, 1982.Google Scholar
  100. 100.
    Martinez-Maza O and Britton S. J Exp Med 157:1808–1814, 1983.Google Scholar
  101. 101.
    Yarchoan R, Tosato G, Blaese RM, Simon RM and Nelson DL. J Exp Med 157:1–14, 1983.Google Scholar
  102. 102.
    Stein LD, Ledgley CJ and Sigal NH. J Immunol 130:1640–1645, 1983.Google Scholar
  103. 103.
    Rosen A and Klein G. Nature 306:189–190, 1983.Google Scholar
  104. 104.
    Steinitz M, Klein G, Koskimies S and Makela O. Nature 269:420–422, 1979.Google Scholar
  105. 105.
    Boyum A. Scand J Clin Invest 21 (Suppl) 97:51–76, 1968.Google Scholar
  106. 106.
    Kozbor D, Steinitz M, Klein G, Koskimies S and Makela O. Scand. J Immunol. 10:187–194, 1979.Google Scholar
  107. 107.
    Steinitz M, Seppala F, Eichman K and Klein G. Immunology 156:41–47, 1979.Google Scholar
  108. 108.
    Koskimies S. Scand J Immunol 10:371, 1979.Google Scholar
  109. 109.
    Crawford DH, Barlow MJ, Harrison JF, Winger L and Huehns ER. Lancet 1:386–388, 1983.Google Scholar
  110. 110.
    Boylston AW, Gardner B, Anderson LR and Hughes-Jones NC. Scand J Immunol 12:355–358, 1980.Google Scholar
  111. 111.
    Steinitz M, Izak G, Cohen S, Ehrenfeld M and Flechner I. Nature 287:443–445, 1980.Google Scholar
  112. 112.
    Tsuchiya S, Yokoyama S, Yoshie O and Ono Y. J Immunol 124:1970–1976, 1980.Google Scholar
  113. 113.
    Kamo I, Furukawa S, Tada A, Mano Y, Iwasaki Y and Furuse T, Science 215:995–997, 1982.Google Scholar
  114. 114.
    Zurawski VR Jr, Black PM and Haber E. Science 199:1439–1441, 1978.Google Scholar
  115. 115.
    Zurawski VR Jr, Black PM and Haber E. In: Monoclonal Antibodies, Hybridomas: A new Dimension in Biological Analyses (Kennett, RH, McKearn TJ and Bechtol KB, eds), pp 19–36. Plenum Press, New York.Google Scholar
  116. 116.
    Ypshie O and Ono, Y. Cell Immunol 56:305–315, 1980.Google Scholar
  117. 117.
    Irie RE, Sze LL and Saxton RE. Proc Natl Acad Sci USA 79:5666–5670, 1982.Google Scholar
  118. 118.
    Watson DB, Burns GF and MacKay IR. J Immunol 130:2442–2447, 1983.Google Scholar
  119. 119.
    Rosén A, Persson K and Klein G. J Immunol 130:2899–2902, 1983.Google Scholar
  120. 120.
    Crawford DH, Callard RE, Muggeridge MI, Mitchell DM, Zanders ED and Beverley PCL. J Gen Virol 64:697–700, 1983.Google Scholar
  121. 121.
    Seigneurin JM, Desgranges C, Seigneurin D, Paire J, Renversez JC, Jacquemont B and Micouin C. Science 221:173–175, 1983.Google Scholar
  122. 122.
    Winger L, Winger C, Shastry P, Russell A and Longenecker M. Proc Natl Acad Sci USA 80:4484–4488, 1983.Google Scholar
  123. 123.
    Ralph P and Kishimoto T. J Clin Invest 68:1093–1096, 1981.Google Scholar
  124. 124.
    Hirohashi S, Shimosato Y and Ino Y. Br J Cancer 46:802–805, 1982.Google Scholar
  125. 125.
    Crawford DH, Huehns ER and Epstein MA. Lancet 1:1040, 1983.Google Scholar
  126. 126.
    Kozbor D and Roder J. Immunol Today 4:72–79.Google Scholar
  127. 127.
    Adams RA, Foley GE, Farber S, Flowers A, Lazarus M and Hellerstein E. Cancer Res 30:338–345, 1970.Google Scholar
  128. 128.
    Giovanella B, Nilsson K, Zech L, Yim O, Klein G and Stehlin J. Int J Cancer 24:103–113, 1979.Google Scholar
  129. 129.
    Abrams PG, Giardina SL, Morgan AC, Oldham RK and Foon KA. Blood 62 (Suppl 1): 186a (abstract), 1983.Google Scholar
  130. 130.
    Freund YR and Blair PB. J Immunol 129:2826–2830, 1982.Google Scholar
  131. 131.
    Habu S, Fukui H, Shimamura K, Kasai M, Nagai Y, Okumura K and Tamaoki N. J Immunol 127:34–38, 1981.Google Scholar
  132. 132.
    Jonak ZL, Braman V and Kennett RH. Hybridoma 2:124 (abstract), 1983.Google Scholar
  133. 133.
    Ochi A, Hawley RG, Shulman M and Hozumi N. Nature 302:340–342, 1983.Google Scholar
  134. 134.
    Oi VT, Morrison SL, Herzenberg LA and Berg P. Proc Natl Acad Sci USA 80:825–829, 1983.Google Scholar
  135. 135.
    Rice D and Baltimore D. Proc Natl Acad Sci USA 79:7862–7865, 1982.Google Scholar
  136. 136.
    Falkner FG and Zachau HG. Nature 298:286–288, 1983.Google Scholar
  137. 137.
    Picard D and Schaffner W. Proc Natl Acad Sci USA 80:417–421, 1983.Google Scholar
  138. 138.
    Gillies SD, Morrison SL, Oi VT and Tonegawa S. Cell 33:717–728, 1983.Google Scholar
  139. 139.
    Neuberger MS. EMBO J 2:1373–1378, 1983.Google Scholar
  140. 140.
    Ochi A, Hawley RG, Hawley T, Shulman M, Traunecker A, Köhler G and Hozumi N. Proc Natl Acad Sci USA 80:6351–6355, 1983.Google Scholar

Copyright information

© Martinus Nijhoff Publishers 1984

Authors and Affiliations

  • S. P. C. Cole
    • 1
  • B. G. Campling
    • 2
  • T. Atlaw
    • 1
  • D. Kozbor
    • 1
  • J. C. Roder
    • 1
  1. 1.Department of Microbiology and ImmunologyQueen's UniversityKingstonCanada
  2. 2.Department of Medicine and Radiation OncologyQueen's UniversityKingstonCanada

Personalised recommendations