Effects of recombinant human interleukin-1 alpha on clonogenic growth of primary human tumors in vitro.
Interleukin-1 alpha (IL-1 alpha) is a low-molecular-weight cytokine that regulates proliferation and differentiation of lymphatic and myeloid cells. It also has pleiotropic activity on a variety of other target cells and acts as an important mediator of inflammation and septic shock. Recombinant human IL-1 alpha (rhIL-1 alpha) is undergoing clinical evaluation of its potential as an anticancer agent. We have studied the growth modulating effects of rhIL-1 alpha on a variety of freshly explanted human tumor specimens using an in vitro soft agar cloning system. Final concentrations of 0.01-100 ng/ml were used in continuous incubation experiments. Of 139 specimens tested, 56 (40%) were evaluable for determination of tumor growth modulating activity. The most common tumor types examined included breast, nonsmall cell lung, ovarian, colorectal cancer, and melanoma. Stimulation of tumor colony-forming units (colony formation greater than or equal to 1.5 x controls) was observed in only 1/56 (2%) tumors. No evidence was found for increased size of individual colonies after incubation with rhIL-1 alpha. At a concentration of 100 ng/ml, colony formation of 9/56 (16%) tumor specimens was significantly inhibited (colony formation less than or equal to 0.5 x controls). We conclude that rhIL-1 alpha is not a major modulator of tumor colony formation in vitro. However, some antitumor effects may be observed at high concentrations.
Hanauske
A R
AR
Technische Universität München, Abteilung Hämatologie und Onkologie, Klinikum rechts der Isar, F.R.G.
Degen
D
D
Marshall
M H
MH
Hilsenbeck
S G
SG
Banks
P
P
Stuckey
J
J
Leahy
M
M
Von Hoff
D D
DD
D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014410:Tumor Stem Cell Assay
D007375:Interleukin-1; D011994:Recombinant Proteins