Abstract
Monoclonal antibodies (Mabs) submitted to the Second International Workshop on Small Cell Lung Cancer Antigens were screened for their ability to mediate the toxic effects of ricin A chain against the NCI-H69 cell line in an indirect assay of immunotoxin cytotoxicity. Cluster 1 Mabs, recognising the neural cell adhesion molecule, mediated little or no cytotoxic effect in combination with screening agent, ricin A chain linked to an antibody Fab' fragment recognising either mouse or rat Mabs. In contrast, cluster 2 Mabs, recognising an epithelial tumour-associated antigen, generally mediated potent cytotoxic effects with the screening agent, inhibiting the incorporation of 3H-leucine by NCI-H69 cells by between 90% and 99%. Measurements of Mab binding to the NCI-H69 cell line by indirect immunofluorescence and flow cytometry indicated that the cluster 2 Mabs generally bound in higher amounts than the cluster 1 Mabs suggesting that the cluster 1 Mabs were ineffective in the screen because they did not bind to the cells in sufficient amounts. However, Mabs recognising antigens other than cluster 1 bound to NCI-H69 cells in amounts similar to those of the cluster 2 Mabs yet did not mediate potent cytotoxic effects in the indirect assay suggesting that the cluster 2 antigen may be internalised in a fashion favouring the delivery of ricin A chain to the cytosol.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- 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]
- Durbin H., Rodrigues N., Bodmer W. F. Further characterization, isolation and identification of the epithelial cell-surface antigen defined by monoclonal antibody AUA1. Int J Cancer. 1990 Mar 15;45(3):562–565. doi: 10.1002/ijc.2910450331. [DOI] [PubMed] [Google Scholar]
- Forrester J. A., McIntosh D. P., Cumber A. J., Parnell G. D., Ross W. C. Delivery of ricin and abrin A-chains to human carcinoma cells in culture following covalent linkage to monoclonal antibody LICR-LOND-Fib 75. Cancer Drug Deliv. 1984 Fall;1(4):283–292. doi: 10.1089/cdd.1984.1.283. [DOI] [PubMed] [Google Scholar]
- Patel K., Moore S. E., Dickson G., Rossell R. J., Beverley P. C., Kemshead J. T., Walsh F. S. Neural cell adhesion molecule (NCAM) is the antigen recognized by monoclonal antibodies of similar specificity in small-cell lung carcinoma and neuroblastoma. Int J Cancer. 1989 Oct 15;44(4):573–578. doi: 10.1002/ijc.2910440402. [DOI] [PubMed] [Google Scholar]
- Till M., May R. D., Uhr J. W., Thorpe P. E., Vitetta E. S. An assay that predicts the ability of monoclonal antibodies to form potent ricin A chain-containing immunotoxins. Cancer Res. 1988 Mar 1;48(5):1119–1123. [PubMed] [Google Scholar]
- 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]
- Weltman J. K., Pedroso P., Johnson S. A., Davignon D., Fast L. D., Leone L. A. Rapid screening with indirect immunotoxin for monoclonal antibodies against human small cell lung cancer. Cancer Res. 1987 Nov 1;47(21):5552–5556. [PubMed] [Google Scholar]