Abstract
The potential of mouse monoclonal antibodies raised against the human small cell lung cancer (SCLC) cell line SW2 to form active immunotoxins was evaluated using an indirect assay of immunotoxin cytotoxicity. Monoclonal antibodies recognising different SCLC-associated antigens, designated as cluster w4 and cluster 5A antibodies by the First International Workshop on SCLC Antigens, mediated the cytotoxic action of a screening agent made by linking ricin A chain to sheep anti-mouse IgG Fab' fragment. In contrast, monoclonal antibodies belonging to cluster 1 gave no significant cytotoxic effects in conjunction with the screening agent. Immunotoxins made by the direct chemical conjugation of ricin A chain to SWA11 (cluster w4) and SWA20 (cluster 5A) both exhibited selective toxic effects upon the SW2 cell line in tissue culture, inhibiting the incorporation of 3H-leucine by 50% at a concentration (IC50) of approximately 3 x 10(-10) M. An immunotoxin made with SEN36 (cluster 1) was much less potent with an IC50 greater than 1 x 10(-8) M.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
- 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]
- Maier A., Schmidt U., Waibel R., Hartung W., Stahel R. A. Expression of the small cell carcinoma antigens of cluster-5 and cluster-5A in primary lung tumours. Br J Cancer. 1989 May;59(5):692–695. doi: 10.1038/bjc.1989.144. [DOI] [PMC free article] [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]
- Smith A., Waibel R., Westera G., Martin A., Zimmerman A. T., Stahel R. A. Immunolocalisation and imaging of small cell cancer xenografts by the IgG2a monoclonal antibody SWA11. Br J Cancer. 1989 Feb;59(2):174–178. doi: 10.1038/bjc.1989.36. [DOI] [PMC free article] [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]
- Waibel R., O'Hara C. J., Smith A., Stahel R. A. Tumor-associated membrane sialoglycoprotein on human small cell lung carcinoma identified by the IgG2a monoclonal antibody SWA20. Cancer Res. 1988 Aug 1;48(15):4318–4323. [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]