Ms. Topp et al., RECOMBINANT HUMAN INTERLEUKIN-4 HAS ANTIPROLIFERATIVE ACTIVITY ON HUMAN TUMOR-CELL LINES DERIVED FROM EPITHELIAL AND NONEPITHELIAL HISTOLOGIES, Cancer research, 55(10), 1995, pp. 2173-2176
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.