Abstract
The specificity of cytotoxic T lymphocytes (Tc) cells is conferred by an antigen-specific receptor, Ti, which in humans is physically associated with an invariant cell-surface glycoprotein, T3 (refs. 1–3). Monoclonal antibodies specific for either T3 and Ti are able to elicit a variety of T-cell responses such as lymphokine production, mitogenesis and cytotoxicity1–11. For example, human Tc cells lyse anti-T3-expressing hybridoma cells, but not cells of other specificity, presumably because anti-T3 on the hybridoma cells binds to T3 on the Tc cells and triggers lysis12. Here, we have adapted approaches used in a different cytotoxic effector system, antibody-dependent cellular cytotoxicity (ADCC), to alter the specificity of Tc cell. Studies of ADCC13 showed that heteroaggregates containing anti-Fc receptor (FcγR) antibody cross-linked to a second antibody bind to FcγR on ADCC effectors and cause them to kill target cells bearing antigen recognized by the second antibody. The present studies use anti-T3-containing heteroaggregates to re-target human Tc cells to cells for which we have appropriate antibodies, including xenogeneic tumour cells and chicken erythrocytes. These results extend previous.observations on the role of T3 in triggering cytotoxicity and suggest that effector cell re-targeting could be used for in vivo treatment of neoplasms and other pathogens that express distinctive surface antigens.
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
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Meuer, S. C., Acuto, O., Hercend, T., Schlossman, S. F. & Reinherz, E. L. A Rev. Immun. 2, 23–50 (1984).
Haskins, K., Kappler, J. & Marrack, P. A. Rev. Immun. 2, 51–66 (1984).
Reinherz, E. L., Meuer, S. C. & Schlossman, S. F. Immun. Rev. 74, 83–112 (1983).
Lancki, D. W., Ma, D. I., Havran, W. L. & Pitch, F. W. Immun. Rev. 81, 65–94 (1984).
von Wussow, P. Platsoucas, C. D. Wiranowska-Stewart, M. & Stewart, W. E. J. Immun. 127, 1197–1200(1981).
Meuer, S. C. et al. J. exp. Med. 158 988–993(1983).
van Wauwe, J. P. De May, J. R. & Goosserts, J. G. J. Immun. 124, 2708–2713 (1980).
Tax, W. J. M., Hermes, F. F. M., Willems, H. W., Capel, P. J. A. & Koene, R. A. P. J. Immun. 133, 1185–1189 (1984).
Kaneoka, H., Perez-Rojas, G., Sasasuki, T., Benike, C. J. & Engelman, E. G. J. Immun. 131, 158–164 (1983).
Kan, E. A. R., Platzer, E., Weite, K. & Wang, C. Y. J. Immun. 133, 2979–2985 (1984).
Kranz, D. M., Tonegawa, S. & Elsen, H. N. Proc. natn. Acad. Sci. U.S.A. 81, 7922–7926 (1984).
Huffman, R. W., Bluestone, J. A., Leo, O. & Shaw, S. J. Immun. (in the press).
Karpovsky, B., Titus, J. A., Stephany, D. A. & Segal, D. M. J. exp. Med. 160, 1686–1701 (1984).
Biddison, W. E., Rao, P. E., Talle, M. A., Goldstein, G. & Shaw, S. J. exp. Med. 159, 783–797 (1984).
Titus, J. A., Sharrow, S. O., Connolly, J. M. & Segal, D. M. Proc. natn. Acad. Sci. U.S.A. 78, 519–523 (1981).
Tsoukas, C. P., Carson, D. A. Fong, S. & Vaughan, J. H. J. Immun. 129, 1421–1425 (1982).
Landegren, U. et al. J. exp. Med. 155, 1579–1584 (1982).
Shaw, S., Goldstein, G., Springer, T. A. & Biddison, W. E. J. Immun. 134, 3019–3026 (1985).
Shaw, S., Johnson, A. H. & Shearer, G. M. J. exp. Med. 152, 565–580 (1980).
Sachs, D. H., Mayer, N. & Ozato, K. in Monoclonal Antibodies and T-Cell Hybridomas (eds Hammerling, G., Hammerling, U. & Kearny, J. F.) 95–101 (Eisevier, New York, 1981).
Unkeless, J. C. J. exp. Med. 150, 580–596 (1979).
Segal, D. M. & Hurwitz, E. Biochemistry 15, 5253–5258 (1976).
Perez, P., Bluestone, J. A., Stephany, D. A. & Segal, D. M. J. Immun. 134, 478–485 (1985).
Staerz, U. D., Kanagawa, O. & Bevan, M. J. Nature 314, 628–631 (1985).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Perez, P., Hoffman, R., Shaw, S. et al. Specific targeting of cytotoxic T cells by anti-T3 linked to anti-target cell antibody. Nature 316, 354–356 (1985). https://doi.org/10.1038/316354a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/316354a0
This article is cited by
-
Safety and efficacy of T-cell-redirecting bispecific antibodies for patients with multiple myeloma: a systematic review and meta-analysis
Cancer Cell International (2023)
-
Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies
Journal of Hematology & Oncology (2021)
-
Multispecific drugs herald a new era of biopharmaceutical innovation
Nature (2020)
-
Bispecific antibodies: a mechanistic review of the pipeline
Nature Reviews Drug Discovery (2019)
-
Targeting CLDN18.2 by CD3 Bispecific and ADC Modalities for the Treatments of Gastric and Pancreatic Cancer
Scientific Reports (2019)
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.
