Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1992 Sep;66(3):444–451. doi: 10.1038/bjc.1992.294

Potent cytotoxic action of the immunotoxin SWA11-ricin A chain against human small cell lung cancer cell lines.

E J Derbyshire 1, R V Henry 1, R A Stahel 1, E J Wawrzynczak 1
PMCID: PMC1977953  PMID: 1325825

Abstract

The cytotoxic activity profile of an immunotoxin, SWA11-ricin A chain, recognising a cell-surface antigen associated with human small cell lung cancer (SCLC), was examined in detail using a panel of SCLC, non-SCLC and non lung tumour cell lines in tissue culture. SWA11-ricin A chain was potently and selectively active against three SCLC cell lines of both classic and variant morphologies, inhibiting the incorporation of 3H-leucine with an IC50 of 5 x 10(-11) M. At a concentration of 1 x 10(-8) M, the SWA11 immunotoxin could selectively eliminate in excess of 99.9% of clonogenic tumour cells. Intoxication proceeded rapidly following a 4 h lag phase; the initial rate of protein synthesis inhibition occurred with a t50 of 2 h and a t10 of 7 h. The cytotoxic activity of SWA11-ricin A chain was potentiated by 100-fold in the presence of the carboxylic ionophore monensin at 1 x 10(-7) M. Kinetic studies revealed that monensin enhanced the rate of protein synthesis inhibition by two-fold and eliminated the lag phase suggesting a rapid effect on either the rate or route of internalisation. Studies with SWA11 could detect no influence of monensin on the rate of antibody internalisation and a transient delay in the delivery of internalised antibody to lysosomes was observed by immunoelectron microscopy.

Full text

PDF
445

Images in this article

449Figure 6
on p.449

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beck L. K., Kane M. A., Bunn P. A., Jr Innovative and future approaches to small cell lung cancer treatment. Semin Oncol. 1988 Jun;15(3):300–314. [PubMed] [Google Scholar]
  2. Bjorn M. J., Ring D., Frankel A. Evaluation of monoclonal antibodies for the development of breast cancer immunotoxins. Cancer Res. 1985 Mar;45(3):1214–1221. [PubMed] [Google Scholar]
  3. Carney D. N., Gazdar A. F., Bepler G., Guccion J. G., Marangos P. J., Moody T. W., Zweig M. H., Minna J. D. Establishment and identification of small cell lung cancer cell lines having classic and variant features. Cancer Res. 1985 Jun;45(6):2913–2923. [PubMed] [Google Scholar]
  4. Carrière D., Casellas P., Richer G., Gros P., Jansen F. K. Endocytosis of an antibody ricin A-chain conjugate (immuno-A-toxin) adsorbed on colloidal gold. Effects of ammonium chloride and monensin. Exp Cell Res. 1985 Feb;156(2):327–340. [PubMed] [Google Scholar]
  5. Casellas P., Bourrie B. J., Gros P., Jansen F. K. Kinetics of cytotoxicity induced by immunotoxins. Enhancement by lysosomotropic amines and carboxylic ionophores. J Biol Chem. 1984 Aug 10;259(15):9359–9364. [PubMed] [Google Scholar]
  6. Casellas P., Jansen F. K. Immunotoxin enhancers. Cancer Treat Res. 1988;37:351–369. doi: 10.1007/978-1-4613-1083-9_19. [DOI] [PubMed] [Google Scholar]
  7. Colombatti M., Dell'Arciprete L., Chignola R., Tridente G. Carrier protein-monensin conjugates: enhancement of immunotoxin cytotoxicity and potential in tumor treatment. Cancer Res. 1990 Mar 1;50(5):1385–1391. [PubMed] [Google Scholar]
  8. Embleton M. J., Byers V. S., Lee H. M., Scannon P., Blackhall N. W., Baldwin R. W. Sensitivity and selectivity of ricin toxin A chain-monoclonal antibody 791T/36 conjugates against human tumor cell lines. Cancer Res. 1986 Nov;46(11):5524–5528. [PubMed] [Google Scholar]
  9. Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
  10. Griffin T. W., Richardson C., Houston L. L., LePage D., Bogden A., Raso V. Antitumor activity of intraperitoneal immunotoxins in a nude mouse model of human malignant mesothelioma. Cancer Res. 1987 Aug 15;47(16):4266–4270. [PubMed] [Google Scholar]
  11. Griffin T., Raso V. Monensin in lipid emulsion for the potentiation of ricin A chain immunotoxins. Cancer Res. 1991 Aug 15;51(16):4316–4322. [PubMed] [Google Scholar]
  12. Hertler A. A., Frankel A. E. Immunotoxins in the therapy of leukemias and lymphomas. Cancer Invest. 1991;9(2):211–219. doi: 10.3109/07357909109044231. [DOI] [PubMed] [Google Scholar]
  13. Hertler A. A., Schlossman D. M., Borowitz M. J., Blythman H. E., Casellas P., Frankel A. E. An anti-CD5 immunotoxin for chronic lymphocytic leukemia: enhancement of cytotoxicity with human serum albumin-monensin. Int J Cancer. 1989 Feb 15;43(2):215–219. doi: 10.1002/ijc.2910430207. [DOI] [PubMed] [Google Scholar]
  14. Klein J. C., Zurcher C., van Bekkum D. W. Differential behavior of human bronchial carcinoma cells in culture. Cancer Res. 1987 Jun 15;47(12):3251–3258. [PubMed] [Google Scholar]
  15. Manske J. M., Buchsbaum D. J., Azemove S. M., Hanna D. E., Vallera D. A. Antigenic modulation by anti-CD5 immunotoxins. J Immunol. 1986 Jun 15;136(12):4721–4728. [PubMed] [Google Scholar]
  16. Monaghan P., Whitehead R. H., Perusinghe N., O'Hare M. J. An immunocytochemical and ultrastructural study of heterogeneity in the human breast carcinoma cell line PMC42. Cancer Res. 1985 Oct;45(10):5088–5097. [PubMed] [Google Scholar]
  17. Postmus P. E., de Ley L., van der Veen A. Y., Mesander G., Buys C. H., Elema J. D. Two small cell lung cancer cell lines established from rigid bronchoscope biopsies. Eur J Cancer Clin Oncol. 1988 Apr;24(4):753–763. doi: 10.1016/0277-5379(88)90311-2. [DOI] [PubMed] [Google Scholar]
  18. Tsai C. M., Ihde D. C., Kadoyama C., Venzon D., Gazdar A. F. Correlation of in vitro drug sensitivity testing of long-term small cell lung cancer cell lines with response and survival. Eur J Cancer. 1990;26(11-12):1148–1152. doi: 10.1016/0277-5379(90)90274-w. [DOI] [PubMed] [Google Scholar]
  19. Vescio R. A., Connors K. M., Bordin G. M., Robb J. A., Youngkin T., Umbreit J. N., Hoffman R. M. The distinction of small cell and non-small cell lung cancer by growth in native-state histoculture. Cancer Res. 1990 Sep 15;50(18):6095–6099. [PubMed] [Google Scholar]
  20. Wawrzynczak E. J., Derbyshire E. J., Henry R. V., Parnell G. D., Smith A., Waibel R., Stahel R. A. Selective cytotoxic effects of a ricin A chain immunotoxin made with the monoclonal antibody SWA11 recognising a human small cell lung cancer antigen. Br J Cancer. 1990 Sep;62(3):410–414. doi: 10.1038/bjc.1990.308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wawrzynczak E. J. Systemic immunotoxin therapy of cancer: advances and prospects. Br J Cancer. 1991 Oct;64(4):624–630. doi: 10.1038/bjc.1991.374. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES