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. 1992 Sep;89(3):336–340. doi: 10.1111/j.1365-2249.1992.tb06958.x

Potentiation of a weakly active ricin A chain immunotoxin recognizing the neural cell adhesion molecule.

E J Derbyshire 1, R A Stahel 1, E J Wawrzynczak 1
PMCID: PMC1554476  PMID: 1325302

Abstract

A ricin A chain immunotoxin, SEN36-ricin A chain, directed against the neural cell adhesion molecule (N-CAM) had no selective cytotoxic activity against three different small cell lung cancer (SCLC) cell lines in tissue culture despite expression of the target antigen on more than 98% of cells in each line detected by indirect immunofluorescence. Treatment of the SW2 SCLC cell line with suramin and interferons alpha and gamma increased the level of N-CAM expression only slightly and had no significant effect on the cytotoxic activity of the SEN36 immunotoxin. In the presence of the carboxylic ionophore monensin at a concentration of 0.1 microM, the toxicity of SEN36-ricin A chain to the SW2 cell line was enhanced by 12,000-fold. In contrast, lysosomotropic amines showed little or no potentiation of activity, suggesting that lysosomal degradation was not the major factor limiting the action of the anti-N-CAM immunotoxin. The findings of this study indicate that ricin A chain immunotoxins directed against N-CAM on SCLC are unlikely to have sufficient activity to be useful therapeutic agents in the absence of potentiating agents such as monensin, which can interfere with the normal intracellular pathways of antigen routing.

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Selected References

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  1. Beverley P. C., Olabiran Y., Ledermann J. A., Bobrow L. G., Souhami R. L. Results of the central data analysis. Br J Cancer Suppl. 1991 Jun;14:10–19. [PMC free article] [PubMed] [Google Scholar]
  2. Carbone D. P., Koros A. M., Linnoila R. I., Jewett P., Gazdar A. F. Neural cell adhesion molecule expression and messenger RNA splicing patterns in lung cancer cell lines are correlated with neuroendocrine phenotype and growth morphology. Cancer Res. 1991 Nov 15;51(22):6142–6149. [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. Chiron M., Jaffrezou J. P., Carayon P., Bordier C., Roubinet F., Xavier C., Brandely M., Laurent G. Induction and increase of HLA-DR antigen expression by immune interferon on ML-3 cell line enhances the anti-HLA-DR immunotoxin activity. Clin Exp Immunol. 1990 Nov;82(2):214–220. doi: 10.1111/j.1365-2249.1990.tb05429.x. [DOI] [PMC free article] [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. Cumber A. J., Forrester J. A., Foxwell B. M., Ross W. C., Thorpe P. E. Preparation of antibody-toxin conjugates. Methods Enzymol. 1985;112:207–225. doi: 10.1016/s0076-6879(85)12018-5. [DOI] [PubMed] [Google Scholar]
  9. Derbyshire E. J., Wawrzynczak E. J. Monoclonal antibodies recognising the cluster 2 antigen associated with human small cell lung cancer mediate the toxic effects of ricin A chain in an indirect assay of immunotoxin cytotoxicity. Br J Cancer Suppl. 1991 Jun;14:74–77. [PMC free article] [PubMed] [Google Scholar]
  10. Edelman G. M. Cell adhesion molecules in the regulation of animal form and tissue pattern. Annu Rev Cell Biol. 1986;2:81–116. doi: 10.1146/annurev.cb.02.110186.000501. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Guo X. J., Fantini J., Roubin R., Marvaldi J., Rougon G. Evaluation of the effect of suramin on neural cell growth and N-CAM expression. Cancer Res. 1990 Aug 15;50(16):5164–5170. [PubMed] [Google Scholar]
  14. 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]
  15. Kruse J., Mailhammer R., Wernecke H., Faissner A., Sommer I., Goridis C., Schachner M. Neural cell adhesion molecules and myelin-associated glycoprotein share a common carbohydrate moiety recognized by monoclonal antibodies L2 and HNK-1. Nature. 1984 Sep 13;311(5982):153–155. doi: 10.1038/311153a0. [DOI] [PubMed] [Google Scholar]
  16. Krönke M., Schlick E., Waldmann T. A., Vitetta E. S., Greene W. C. Selective killing of human T-lymphotropic virus-I infected leukemic T-cells by monoclonal anti-interleukin 2 receptor antibody-ricin A chain conjugates: potentiation by ammonium chloride and monensin. Cancer Res. 1986 Jul;46(7):3295–3298. [PubMed] [Google Scholar]
  17. Lashford L., Jones D., Pritchard J., Gordon I., Breatnach F., Kemshead J. T. Therapeutic application of radiolabeled monoclonal antibody UJ13A in children with disseminated neuroblastoma. NCI Monogr. 1987;(3):53–57. [PubMed] [Google Scholar]
  18. Laurent G., Kuhlein E., Casellas P., Canat X., Carayon P., Poncelet P., Correll S., Rigal F., Jansen F. K. Determination of sensitivity of fresh leukemia cells to immunotoxins. Cancer Res. 1986 May;46(5):2289–2294. [PubMed] [Google Scholar]
  19. Miraldi F. D., Nelson A. D., Kraly C., Ellery S., Landmeier B., Coccia P. F., Strandjord S. E., Cheung N. K. Diagnostic imaging of human neuroblastoma with radiolabeled antibody. Radiology. 1986 Nov;161(2):413–418. doi: 10.1148/radiology.161.2.3763911. [DOI] [PubMed] [Google Scholar]
  20. Patel K., Bourne S., Phimister B., Coakham H., Kemshead J. T. Presence of neural cell adhesion molecule on human embryonic and brain tumours. Biochem Soc Trans. 1990 Jun;18(3):408–410. doi: 10.1042/bst0180408. [DOI] [PubMed] [Google Scholar]
  21. Pearson J. W., Hedrick E., Fogler W. E., Bull R. L., Ferris D. K., Riggs C. W., Wiltrout R. H., Sivam G., Morgan A. C., Groves E. Enhanced therapeutic efficacy against an ovarian tumor xenograft of immunotoxins used in conjunction with recombinant alpha-interferon. Cancer Res. 1990 Oct 1;50(19):6379–6388. [PubMed] [Google Scholar]
  22. 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]
  23. Ramakrishnan S., Bjorn M. J., Houston L. L. Recombinant ricin A chain conjugated to monoclonal antibodies: improved tumor cell inhibition in the presence of lysosomotropic compounds. Cancer Res. 1989 Feb 1;49(3):613–617. [PubMed] [Google Scholar]
  24. Ruff M. R., Farrar W. L., Pert C. B. Interferon gamma and granulocyte/macrophage colony-stimulating factor inhibit growth and induce antigens characteristic of myeloid differentiation in small-cell lung cancer cell lines. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6613–6617. doi: 10.1073/pnas.83.17.6613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wawrzynczak E. J., Derbyshire E. J., Henry R. V., Parnell G. D., Smith A., Waibel R., Stahel R. A. Cytotoxic activity of ricin A chain immunotoxins recognising cluster 1, w4 and 5A antigens associated with human small cell lung cancer. Br J Cancer Suppl. 1991 Jun;14:71–73. [PMC free article] [PubMed] [Google Scholar]
  26. 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]

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