Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Reshaping human antibodies for therapy

Abstract

A human IgGI antibody has been reshaped for serotherapy in humans by introducing the six hypervariable regions from the heavy- and light-chain variable domains of a rat antibody directed against human lymphocytes. The reshaped human antibody is as effective as the rat antibody in complement and is more effective in cell-mediated lysis of human lymphocytes.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Behring, E. von & Kitasato, S. Dtsch. Med. Wochenschr. 16, 1113–1114 (1890).

    Article  Google Scholar 

  2. 2

    Ratner, B. Allergy Anaphylaxis and Immunotherapy (Williams and Wilkins, Baltimore, 1943).

    Google Scholar 

  3. 3

    Kohler, G. & Milstein, C. Nature 256, 495–497 (1975).

    ADS  CAS  Article  Google Scholar 

  4. 4

    Ehrlich, P. in Immunology and Cancer Research vol. 2 (ed. Himmelweit, F.) (Pergamon, London, 1957).

    Google Scholar 

  5. 5

    Deland, F. H. & Goldenberg, D. M. in Radionuclide Imaging (ed. Kuhl, D. E.) 289–307 (Pergamon, Paris, 1982).

    Google Scholar 

  6. 6

    Levy, R. & Miller, R. A. A. Rev. Med. 34, 107–116 (1983).

    CAS  Article  Google Scholar 

  7. 7

    Miller, R. A., Oseroff, A. R., Stratte, P. T. & Levy, R. Blood 62, 988–995 (1983).

    CAS  PubMed  Google Scholar 

  8. 8

    Leung, D. Y. M., Rosen, & Geha, R. S. in Primary and Secondary Immunodeficiency Disorders (ed. Chandra, R. K.) 44–61 (Churchill Livingstone, New York, 1983).

    Google Scholar 

  9. 9

    Carson, D. A. & Freimark, B D. Adv. Immun. 38, 275–311 (1986).

    CAS  Article  Google Scholar 

  10. 10

    Morrison, S. L., Johnson, M. J., Herzenberg, S. A. & Oi, V. T. Proc. natn. Acad. Sci. U.S.A. 81, 6851–6855 (1984).

    ADS  CAS  Article  Google Scholar 

  11. 11

    Boulianne, G. L., Hozumi, N. & Shulman, M. J. Nature 312, 643–646 (1984).

    ADS  CAS  Article  Google Scholar 

  12. 12

    Neuberger, M. S. et al. Nature 314, 268–270 (1985).

    ADS  CAS  Article  Google Scholar 

  13. 13

    Liu, A. Y. et al. Proc. natn. Acad. Sci. U.S.A. 84, 3439–3443 (1987).

    ADS  CAS  Article  Google Scholar 

  14. 14

    Shaw, D. R. et al. J. Immun. 138, 4534–4538 (1987).

    CAS  PubMed  Google Scholar 

  15. 15

    Bruggemann, M. et al. J. exp. Med. 166, 1351–1361 (1987).

    CAS  Article  Google Scholar 

  16. 16

    Hale, G., Swirsky, D. M., Hayhoe, F. G. J. & Waldmann, H. Molec. biol. Med. 1, 321–334 (1983).

    CAS  PubMed  Google Scholar 

  17. 17

    Giorgi, J. V. et al. Transplantn Proc. 15, 639–642 (1983).

    Google Scholar 

  18. 18

    Benjamin, R., Cobbold, S. P., Clark, M. R. & Waldmann, H. J. exp. Med. 163, 1539–1552 (1986).

    CAS  Article  Google Scholar 

  19. 19

    Jones, P. T., Dear, P. H., Foote, J., Neuberger, M. S. & Winter, G. Nature 321, 522–525 (1986).

    ADS  CAS  Article  Google Scholar 

  20. 20

    Hale, G. et al. Blood 62, 873–882 (1983).

    CAS  Google Scholar 

  21. 21

    Hale, G., Hoang, T., Prospero, T., Watt, S. M. & Waldmann, H. Molec. biol. Med. 1, 305–319 (1983).

    CAS  PubMed  Google Scholar 

  22. 22

    Hale, G. et al. J. Immun. Meth. 103, 59–67 (1987).

    CAS  Article  Google Scholar 

  23. 23

    Hale, G., Waldmann, H., Friend, P. & Calne, R. Transplantation 42, 308–311 (1986).

    CAS  Article  Google Scholar 

  24. 24

    Hale, G., Swirsky, D. M., Hayhoe, F. G. J. & Waldmann, H. Molec. biol. Med. 1, 321–334 (1983).

    CAS  PubMed  Google Scholar 

  25. 25

    Kabat, E. A., Wu, T. T., Reid-Miller, M., Perry, H. M. & Gottesman, K. S. in Sequences of Proteins of Immunological Interest (US Dept. of Health and Human Services, US Government Printing Office, 1987).

    Google Scholar 

  26. 26

    Chothia, C., Novotny, J., Bruccoleri, R. & Karplus, M. J. J. molec. Biol. 186, 651–663 (1985).

    CAS  Article  Google Scholar 

  27. 27

    Saul, F. A., Amzel M. & Poljak, R. J. J. biol. Chem. 253, 585–597 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28

    Epp, O. et al. Eur. J. Biochem. 45, 513–524 (1974).

    CAS  Article  Google Scholar 

  29. 29

    Mulligan, R. C. & Berg, P. Proc. natn. Acad. Sci. U.S.A. 78, 2072–2076 (1981).

    ADS  CAS  Article  Google Scholar 

  30. 30

    Southern, P. J. & Berg, P. J. molec. appl. Genetics 1, 327–3451 (1981).

    Google Scholar 

  31. 31

    Galfre, G. & Milstein, C. Meth. Enzym. 73, 1–46 (1981).

    Google Scholar 

  32. 32

    Chothia, C. & Lesk, A. J. Mol. Biol. 196, 901–917 (1987).

    CAS  Article  Google Scholar 

  33. 33

    Roberts, S., Cheetham, J. C. & Rees, A. R. Nature 328, 731–734 (1987).

    ADS  CAS  Article  Google Scholar 

  34. 34

    Junker, M. & den Brok, J. H. A. M. Eur. J. Immun. 17, 1547–1552 ( 1987).

    Article  Google Scholar 

  35. 35

    Clark, M. & Waldmann, H. J.N.C.I. 79, 1393–1398 (1987).

    CAS  Google Scholar 

  36. 36

    Hieter, P. A., Max, E. E., Seidmann, J. G., Maizel, J. V. Jr & Leder, P. Cell 22, 197–207 (1980).

    CAS  Article  Google Scholar 

  37. 37

    Kaartinen, M. et al. J. Immun. 130, 320–324 (1983).

    Google Scholar 

  38. 38

    Gubier, U. & Hoffmann, B. J. Gene 25, 263–269 (1983).

    Article  Google Scholar 

  39. 39

    Sanger, F., Nicklen, S. A. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).

    ADS  CAS  Article  Google Scholar 

  40. 40

    Takahashi, N., Ueda, N. S., Obata, M., Nikaido, T. & Honjo, T. Cell 29, 671–679 (1982).

    CAS  Article  Google Scholar 

  41. 41

    Flanagan, J. G. & Rabbits, T. H. Nature 300, 709–713 (1982).

    ADS  CAS  Article  Google Scholar 

  42. 42

    Huck, S., Fort, P., Crawford, D. H., Lefranc, M.-P. & Lefranc, G. Nucleic Acids Res. 14, 1779–1789 (1986).

    CAS  Article  Google Scholar 

  43. 43

    Bruggemann, M. et al. Proc. natn. Acad. Sci. U.S.A. 83, 6075–6079 (1986).

    ADS  CAS  Article  Google Scholar 

  44. 44

    Potter, H., Weir, L. & Leder, P. Proc. natn. Acad. Sci. U.S.A. 81, 7161–7163 (1984).

    ADS  CAS  Article  Google Scholar 

  45. 45

    Marquardt, M., Deisenhofer, J., Huber, R. & Palm, W. J. molec. Biol. 141, 369–391 (1980).

    Article  Google Scholar 

  46. 46

    Hale, G., Clark, M. & Waldmann, H. J. Immun. 123, 3056–3061 (1985).

    Google Scholar 

  47. 47

    Verhoeyen, M., Milstein, C. & Winter, G. Science (in the press).

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Riechmann, L., Clark, M., Waldmann, H. et al. Reshaping human antibodies for therapy. Nature 332, 323–327 (1988). https://doi.org/10.1038/332323a0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing