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

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Summary

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.

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Authors and Affiliations

  1. Drug Targeting Laboratory, Section of Immunology, Institute of Cancer Research, SM2 5NG, Sutton, Surrey, UK

    Elaine J. Derbyshire & Edward J. Wawrzynczak

  2. Division of Oncology, University Hospital, CH-8091, Zurich, Switzerland

    Rolf A. Stahel

Authors
  1. Elaine J. Derbyshire
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  2. Rolf A. Stahel
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  3. Edward J. Wawrzynczak
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Derbyshire, E.J., Stahel, R.A. & Wawrzynczak, E.J. Cytotoxic properties of a ricin A chain immunotoxin recognising the cluster-5A antigen associated with human small-cell lung cancer. Cancer Immunol Immunother 35, 417–420 (1992). https://doi.org/10.1007/BF01789021

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  • DOI: https://doi.org/10.1007/BF01789021

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