An anti-mucin immunotoxin BrE-3-ricin A-chain is potently and selectively toxic to human small-cell lung cancer
✍ Scribed by Elaine J. Derbyshire; Edward J. Wawrzynczak
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- French
- Weight
- 814 KB
- Volume
- 52
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
Monoclonal antibodies (MAbs) known to recognize epithelial much or defined carbohydrate structures present on much molecules were screened for their ability to form cytotoxic agents with ricin A-chain active against human small-cell lung cancer (SCLC) in an indirect assay of immunotoxin cytotoxicity.
Anti-X hapten and anti-Y hapten antibodies binding to a high proportion of SCLC cells mediated only weak to moderate effects on 3H-leucine incorporation in combination with
the screening agent, sheep anti-mouse IgG FL-ricin A-chain. In contrast, the mouse MAb BrE-3, recognizing the polypeptide core of the MUCl mucin gene product, exerted potent and selective cytotoxic effects in the assay. An immunotoxin made by the direct attachment of ricin A-chain to BrE-3 was selectively toxic to SCLC cell lines in tissue culture. The cytotoxic activity of BrE-3-ricin A-chain was enhanced 100-fold in the presence of monensin but not by lysosomotropic amines or calcium antagonists. Our findings suggest that anti-mucin immunotoxins may have a therapeutic role to play in the treatment of SCLC. o 1992 Wiley-Liss, 1nc.