Cytotoxins Directed at Interleukin-4 Receptors as Therapy for Human Brain Tumors

Interleukin-4 (IL-4) is a pleiotropic immune regulatory cytokine that has been extensively studied in the last decade. Activated T-lymphocytes, mast cells, and basophils (1 –3 ) produce it. Consistent with the pleiotropic nature of this molecule, the receptors for IL-4 have been identified on many different cell types, including hematopoietic and nonhematopoietic cells (2 –4 ). We have reported that a variety of solid tumor cells express a greater number of highaffinity IL-4 receptors (IL-4R) than normal cells (5 –12 ). We were first to report that murine solid cancer cells expressed high affinity IL-4R (4 ). We later reported that human renal-cell carcinoma and other solid tumor cells expressed functional IL-4R (6 –7 ). These receptors are functional because IL-4 can cause signal transduction, inhibit growth of some tumor cell lines, and increase expression of major histocompatibility antigens and the intercellular adhesion molecule-1 (ICAM-1) on some tumor cell lines (11 –17 ). IL-4R is also expressed, although in low numbers, in normal immune cells such as T-cells, B-cells, monocytes, other blood cells such as eosinophils, basophils, and fibroblasts, and endothelial cells (1 –3 ).