Cytotoxic properties of a ricin A chain immunotoxin recognising the cluster-5A antigen associated with human small-cell lung cancer.
The cytotoxic properties of a ricin A chain immunotoxin made with the mouse monoclonal antibody SWA20, recognising a family of sialoglycoprotein antigens selectively expressed by human small-cell lung cancer (SCLC), were examined using a panel of tumour cell lines in tissue culture. SWA20-ricin-A-chain was selectively toxic to the SW2, NCI-H69 and GLC-8 SCLC cell lines, inhibiting the incorporation of [3H]leucine by 50% at a concentration of 0.2-2 nM, but had no selective activity against the NCI-H23 and NCI-H125 lung adenocarcinoma or the control CEM T-lymphoblastoid cell lines. The SWA20 immunotoxin intoxicated the SW2 cell line rapidly, inhibiting [3H]leucine incorporation by 50% within 2 h compared with 0.5 h for ricin. Analysis of the effects of SWA20-ricin-A-chain on the growth of SW2 cells using a limiting-dilution clonogenic assay revealed that the immunotoxin could eliminate 95% of clonogenic malignant cells. Although SWA20-ricin-A-chain was found to be rapidly active against the majority of tumour cells, its action was limited by the presence of insensitive cells expressing low levels of the target antigen.
Derbyshire
E J
EJ
Drug Targeting Laboratory, Institute of Cancer Research, Sutton, Surrey, UK.
Stahel
R A
RA
Wawrzynczak
E J
EJ
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D018288:Carcinoma, Small Cell / Q000276:immunology*; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000276:immunology*; D012276:Ricin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000922:Immunotoxins; D012276:Ricin