Abstract
ANTIBODIES and growth factors have been chemically coupled to different toxins to produce cytotoxic molecules that selectively kill cells bearing appropriate antigens or receptors1,2. Antibody-toxin conjugates (immunotoxins) produced using conventional chemical coupling techniques have several undesirable characteristics. The smallest binding unit of an antibody is an Fv fragment which consists of a light and heavy chain variable domain. Recently, active single chain Fv fragments of antibodies have been produced in Esherichia coli x by attaching the light and heavy chain variable domains together with a peptide linker3,4. Here we describe the construction and expression in E coli. of a single chain antibody toxin fusion protein, anti-Tac(Fv)–PE40, in which the variable regions of anti-Tac, a monoclonal antibody to the p55 subunit of the human interleukin-2 receptor5, are joined in peptide linkage to PE40, a modified form of Pseudomonas exotoxin lacking its binding domain. Anti-Tac(Fv)–PE40 was very cytotoxic to two interleukin-2 receptor-bearing human cell lines but was not cytotoxic to receptor-negative cells.
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
Pastan, I., Willingham, M. C. & FitzGerald, D. J. Cell 47, 641–648 (1986).
Vitetta, E. S., Fulton, R. J., May, R. D., Till, M. & Uhr, J. W. Science 238, 1098–1104 (1987).
Bird, R. E. et al. Science 242, 423–426 (1988).
Houston, J. S. et al. Proc. natn. Acad. Sci. U.S.A. 85, 5879–5883 (1988).
Uchiyama, T., Broder, S. & Waldmann, T. A. J. Immuno. 126, 1393–1397 (1981).
Chaudhary, V. K., FitzGerald, D. J., Adhya, S. & Pastan, I. Proc. natn. Acad. Sci. U.S.A. 84, 4538–4542 (1987).
Lorberboum-Galski, H., FitzGerald, D., Chaudhary, V., Adhya, S. & Pastan, I. Proc. natn. Acad. Sci. U.S.A. 85, 1922–1926 (1988).
Chaudhary, V. K. et al. Nature 335, 369–372 (1988).
Siegall, C. B., Chaudhary, V. K., FitzGerald, D. J. & Pastan, I. Proc. natn. Acad. Sci. U.S.A. 85, 9738–9742 (1988).
Bacha, P., et al. Proc. natn. Acad. Sci. U.S.A. 167, 612–622 (1988).
Studier, F. W. & Moffat, B. A. J. molec. Biol. 189, 113–130 (1986).
Willingham, M. C., FitzGerald, D. J., & Pastan, I. Proc. natn. Acad. Sci. U.S.A. 84, 2474–2478 (1987).
Salahuddin, S. Z. et al. Virology 129, 51–64 (1983).
Kondo, T., FitzGerald, D., Chaudhary, V., Adhya, S., & Pastan, I. J. biol. Chem. 263, 9470–9475 (1988).
FitzGerald, D. J. P., Waldmann, T. A., Willingham, M. C. & Pastan, I. J. clin. Invest. 74, 966–971 (1984).
Robb, R. J., Green, W. G., & Rusk, C. M. J. exp. Med. 160, 1126–1146 (1984).
Hwang, J., FitzGerald, D. J. P., Adhya, S. & Pastan, I. Cell 48, 129–136 (1987).
Laemmli, U. K. Nature 227, 680–685 (1970).
Berzofsky, J. A. & Schechter, A. N. Molec. Immun. 18, 751–763 (1981).
Bradford, M. M. Analyt. Biochem. 72, 248–254 (1976).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chaudhary, V., Queen, G., Junghans, R. et al. A recombinant immunotoxin consisting of two antibody variable domains fused to Pseudomonas exotoxin. Nature 339, 394–397 (1989). https://doi.org/10.1038/339394a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/339394a0
This article is cited by
-
Novel bacterial ADP-ribosylating toxins: structure and function
Nature Reviews Microbiology (2014)
-
The development of immunoconjugates for targeted cancer therapy
Nature Reviews Clinical Oncology (2014)
-
Hairy Cell Leukemia—New Genes, New Targets
Current Hematologic Malignancy Reports (2013)
-
Purification of clinical-grade disulfide stabilized antibody fragment variable—Pseudomonas exotoxin conjugate (dsFv-PE38) expressed in Escherichia coli
Applied Microbiology and Biotechnology (2013)
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.