Nonspecific Cytotoxicity of Recombinant Interleukin-2 Activated Lymphocytes

• Published in: The American journal of the medical sciences 1989-07, Vol.298 (1), p.28-33
• Main Authors: Bechard, Daniel E., Gudas, Stephen A., Sholley, Milton M., Grants, Angus J., Merchant, Randall E., Fairman, R. Paul, Fowler, Alpha A., Glauser, Frederick L.
• Format: Article
• Language: English
• Subjects: Activated Lymphocytes; Animals; Biological and medical sciences; Cattle; Cytotoxic reactions (adcc reaction, cell-mediated lympholysis, complement-dependent cytotoxicity and others); Cytotoxicity; Cytotoxicity, Immunologic - drug effects; Free Radicals; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Immunological reactions in vitro; Interleukin-2 - pharmacology; Interleukin–2; Killer Cells, Natural - drug effects; Killer Cells, Natural - physiology; Lymphocyte Activation; Oxygen - pharmacology; Peptide Hydrolases - pharmacology; Recombinant Proteins; Time Factors; Vascular Leak
• ISSN: 0002-9629; 1538-2990
• DOI: 10.1097/00000441-198907000-00005

The administration of interleukin-2 (IL-2) and lymphokine activated killer (LAK) cells to patients with advanced metastatic cancer has yielded encouraging results. The purported ability of LAK cells to be discriminatively tumorcidal, thus sparing normal host tissue, represents a major advance over conventional chemotherapy. However, IL-2 adoptive immunotherapy results in dose-limiting toxicity characterized by weight gain, dyspnea, ascites, and peripheral-pulmonary edema suggestive of a vascular leak syndrome. It is unclear whether the observed toxicity is directly related to IL-2 and/or LAK cells. The authors examined the cytolytic nature of human LAK cells against human endothelial, epithelial, and fibroblast cell lines. Bovine endothelial cells also were studied. Using a 51Cr release assay, the cytolytic potential, time course, and effect of reactive oxygen intermediate inhibitors were studied. LAK cells were uniformly toxic against all cell lines, in contrast to high dose rIL-2 and excipient. Significant cytolysis was observed within 30 minutes and increased over the first 2 hours of LAK cells coming in contact with target cells. Reactive oxygen intermediate inhibitors did not reduce cytolytic activity. The authors thus found human LAK cells to be rapidly cytolytic against a variety of human and bovine cell lines. This cytolysis was independent of reactive oxygen intermediates.