An anti‐mucin immunotoxin BrE‐3‐ricin A‐chain is potently and selectively toxic to human small‐cell lung cancer

Monoclonal antibodies (MAbs) known to recognize epithelial mucin or defined carbohydrate structures present on mucin 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 F'ab‐ricin A‐chain. In contrast, the mouse MAb BrE‐3, recognizing the polypeptide core of the MUCI 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. © 1992 Wiley‐Liss, Inc.