Cytotoxic properties of a ricin A chain immunotoxin recognising the cluster-5A antigen associated with human small-cell lung cancer

Abstract

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.

Immunotoxin Therapy for Lung Cancer

“…[50515253] The mouse mAb BrE-3 targeting the polypeptide core of antigen MUC1[54] is combined with RTA to form another immunotoxin, which has been reported to be effective in SCLC. [55]…”

Expression of the coxsackie adenovirus receptor in neuroendocrine lung cancers and its implications for oncolytic adenoviral infection

“…Human SCLC cell lines OH1 (classic phenotype), 19,20 OH3 (classic phenotype), 19,21 H69 (classic phenotype), 22,23 H82 (variant phenotype), 19,23 which were all established from pleural effusions and SW2 (variant phenotype), 22,24 established from a bone marrow metastasis were propagated in Dulbecco's modification of Eagle's medium (PAA Laboratories, Pasching, Austria) for adenovirus infections. For TSA stimulation, cells were cultivated in RPMI 1640 (Gibco, Scotland, UK).…”

Immunotoxins recognising a new epitope on the neural cell adhesion molecule have potent cytotoxic effects against small cell lung cancer

“…Both bR and PE blocked by a thioether linkage have intact translocation and catalytic domains. If a target antigen is internalised by the cell modification can be accomplished through removal of the B-chain of ricin (Blakey & Thorpe, 1988) or through genetically deleting domain I of PE (Pastan & FitzGerald, 1991 (Wawrzynczak et al, 1990;Derbyshire et al, 1992a;Zangemeister-Wittke et al, 1993a,b) as well as in the clinic (Lynch et al, 1993).…”