One approach to the selective destruction of tumor cells in heterogeneous cell populations is to use specific receptors to localize cytotoxic or potentially cytotoxic molecules. Since basophilic leukemia cells, as well as mast cells and basophils, frequently or invariably contain IgE receptors, it should be possible to use IgE immunoglobulin as a cytotoxic carrier for the ablation of these cells. With rat basophilic leukemia (RBL-1) cells as the target, selective cytotoxicity was accomplished by the use of rat IgE conjugated to biotin followed by avidin (which has affinity for biotin) coupled to a cytotoxic enzyme system composed of an avidin-glucose oxidase conjugate (Av-GO) and the cofactors lactoperoxidase and iodide. Greater than 90% cell killing was obtained by using as little as 0.2 μg/ml Av-GO. The addition of free biotin or the exclusion of IgE-biotin, Av-GO, or cofactors from the complete system reduced cytotoxicity to 7 to 40% of control values and the substitution of unconjugated Av and GO for Av-GO caused no killing, demonstrating the requirement for each component of the specific cytotoxic system. In addition to its potential as a model and possibly practical system for the induction of enzyme amplified affinity cytotoxicity in neoplastic cells, this cytotoxic system may be of value in the selection of variant cell lines with mutant or absent IgE receptors in the study of IgE-cell receptor interactions.
|Number of pages||9|
|Journal||Journal of Immunology|
|State||Published - Jan 1 1980|