NOVEL WAY TO INCREASE TARGETING SPECIFICITY TO A HUMAN GLIOBLASTOMA-ASSOCIATED RECEPTOR FOR INTERLEUKIN-13

Human brain cancers (gliomas) overexpress large numbers of a receptor for interleukin 13 (IL13), making this receptor an attractive target f or anti-glioma therapies. We have recently proposed that the glioma-as sociated IL13 receptor is different from the one expressed on some hem opoietic and somatic cells. In an attempt to identify an even more gli oma-specific target, we have used an antagonist of a related cytokine, IL4, which neutralizes the physiological effects of both IL13 and IL4 on normal cells. Here we demonstrate that the IL4 antagonist also cou nteracts the action of cytotoxins targeted to the IL13 receptor on nor mal human cells. Importantly, the IL4 antagonist does not inhibit IL13 -based cytotoxins on glioma cells at all. Thus, the IL13 receptor on g lioma cells can be categorized as tumor-specific in the presence of an IL4 antagonist. We conclude that IL13 receptor-directed cytotoxins ca n be delivered to glioma cells without being cytotoxic to normal cells . (C) 1998 Wiley-Liss, Inc.