RECOMBINANT HUMAN INTERLEUKIN-4 HAS ANTIPROLIFERATIVE ACTIVITY ON HUMAN TUMOR-CELL LINES DERIVED FROM EPITHELIAL AND NONEPITHELIAL HISTOLOGIES

Interleukin 4, a T cell-derived 20-kDa glycoprotein, plays an importan t role in regulating the immune response of B cells, T cells, and macr ophages against infections and malignant cells. For this reason recomb inant human interleukin 4 (rhIL-4) has entered early clinical trials i n cancer patients. In the present study we report that rhIL-4 has an a ntiproliferative effect on five of nine cell lines derived from human colon tumors, head and neck tumors, and glioblastomas as measured by a decrease of colony formation in human tumor cloning assays. All of th e cell lines with in vitro responsiveness express at least 100 high-af finity receptors for human interleukin 4 per cell on their cell surfac e, whereas the nonresponsive tumor cell lines lack expression of high- affinity receptors for human interleukin 4 on their cell surface. In t he next series of experiments we have xenotransplanted some of the res ponsive cell lines into athymic nude mice, Subsequently, the animals w ere treated s.c. twice daily with 0.5 mg/m(2) rhIL-4 or control vehicl e for at least 12 days. There was a clear growth inhibition of these x enotransplanted tumors in the mice treated with rhIL-4. Histology of t he tumors in both groups revealed no marked infiltration with murine h ematopoietic and lymphocytic cells as evaluated by staining with a rat anti-mouse CD45 antibody. We conclude that rhIL-4 has a direct therap eutic activity on the growth of some human epithelial and nonepithelia l tumor cell lines which, along with its regulatory function on hemato lymphopoietic cells, makes this cytokine an interesting candidate for experimental tumor therapy.