Hybrid antibodies can target sites for attack by T cells (original) (raw)

Nature volume 314, pages 628–631 (1985)Cite this article

Abstract

It would be advantageous in the case of certain diseases to be able to focus a strong T-cell response at a chosen target, for example, in treating cancer or infections that have escaped the normal host response. At present, it seems inconceivable that we could use antigen-specific lines or clones of effector T cells for this purpose because of complications due to the major histocompatibility restriction of T-cell specificity and the problem of rejection of transplanted effector cells. Here we describe a novel technology which combines the power of T lymphocytes in eliminating unwanted cells and causing beneficial inflammatory reactions with the great advantages of monoclonal antibodies (their specificity and availability). We show that heteroconjugates of monoclonal antibodies (referred to hereafter as hybrid antibodies), in which one of the component binding sites is anti-T-cell receptor and the other component binding site is directed against any chosen target antigen, can focus T cells to act at the targeted site. Monoclonal antibodies directed against the T-cell receptor, such as the anti-allotype used here, are mitogenic for resting T cells and can be used to induce effector T cells carrying the T-cell receptor determinant which can then be directed against the target by a hybrid antibody.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 51 print issues and online access

$199.00 per year

only $3.90 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

References

  1. Kappler, J., Kubo, R., Haskins, K., White, J. & Marrack, P. Cell 34, 727–737 (1983).
    Article CAS PubMed Google Scholar
  2. Meuer, S. C. et al. J. exp. Med. 158, 988–993 (1983).
    Article CAS PubMed Google Scholar
  3. Staerz, U. D., Pasternack, M. S., Klein, J. R., Benedetto, J. D. & Bevan, M. J. Proc. natn. Acad. Sci. U.S.A. 81, 1799–1803 (1984).
    Article ADS CAS Google Scholar
  4. Kaye, J., Porcelli, S., Tite, J., Jones, B. & Janeway, C. A. J. exp Med. 158, 836–856 (1983).
    Article CAS PubMed Google Scholar
  5. Ertl, H. et al. Proc. natn. Acad. Sci. U.S.A. 79, 7479–7483 (1982).
    Article ADS CAS Google Scholar
  6. Lancki, D. W. & Fitch, F. W. Fedn Proc. 43, 1659 (1984).
    Google Scholar
  7. Martz, E. Immun. Today 5, 254–255 (1984).
    Article CAS PubMed Google Scholar
  8. Staerz, U. D., Rammensee, H.-G., Benedetto, J. D. & Bevan, M. J. J. Immun. (in the press).
  9. Haskins, K. et al. J. exp. Med. 160, 452–471 (1984).
    Article CAS PubMed Google Scholar
  10. Roehm, N. et al. Cell 38, 577–584 (1984).
    Article CAS PubMed Google Scholar
  11. Houston, L. L., Nowinski, R. C. & Bernstein, I. D. J. Immun. 125, 837–843 (1980).
    CAS PubMed Google Scholar
  12. Staerz, U. D. & Bevan, M. J. ICSU Short Rep. 2 (in the press).
  13. Bevan, M. J. & Cohn, M. J. Immun. 114, 559–565 (1975).
    CAS PubMed Google Scholar
  14. Marshak-Rothstein, A. et al. J. Immun. 122, 2491–2497 (1979).
    CAS PubMed Google Scholar
  15. Ozato, K. & Sachs, D. J. Immun. 126, 317–321 (1981).
    CAS PubMed Google Scholar
  16. Carlsson, J., Drevin, H. & Axen, R. Biochem. J. 173, 723–737 (1978).
    Article CAS PubMed PubMed Central Google Scholar
  17. Jou, Y.-H. & Bankert, R. B. Proc. natn. Acad. Sci. U.S.A. 78, 2493–2496 (1981).
    Article ADS CAS Google Scholar
  18. Chen, S.-S. & Katz, D. H. J. exp. Med. 157, 772–788 (1983).
    Article CAS PubMed Google Scholar

Download references

Author information

Authors and Affiliations

  1. Department of Immunology, Scripps Clinic and Research Foundation, 10666 North Torrey Pines Road, La Jolla, California, 92037, USA
    Uwe D. Staerz & Michael J. Bevan
  2. Lilly Research Laboratories, 3252 Holiday Court, Suite 101, La Jolla, California, 92037, USA
    Osami Kanagawa

Authors

  1. Uwe D. Staerz
    You can also search for this author inPubMed Google Scholar
  2. Osami Kanagawa
    You can also search for this author inPubMed Google Scholar
  3. Michael J. Bevan
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Staerz, U., Kanagawa, O. & Bevan, M. Hybrid antibodies can target sites for attack by T cells.Nature 314, 628–631 (1985). https://doi.org/10.1038/314628a0

Download citation