Journal of Clinical Oncology, Vol 1, 217-225, Copyright © 1983 by American Society of Clinical Oncology
Effects of cloned human leukocyte interferons in the human tumor stem cell assay
SE Salmon, BG Durie, L Young, RM Liu, PW Trown and N Stebbing
Clonogenic tumor cells from fresh biopsies of human cancers were cultivated
in vitro and tested for sensitivity by continuous exposure to
pharmacologically achievable concentrations of either of two highly
purified human leukocyte interferon subtypes (IFN-alpha A and IFN-alpha D)
prepared by recombinant DNA methods. The interferons were compared on a
weight basis at concentrations of 0.4 and 4.0 ng/ml (equivalent to 80 and
800 units of interferon activity for IFN-alpha A and 2.0 and 20 units for
IFN-alpha D). Inhibition of tumor colony-forming units (50% of control or
less) was observed in 38.1% of the 273 tumors tested against IFN-alpha A,
and in 16% of the 71 tumors tested against IFN- alpha D. Of the tumor types
with at least ten samples tested against IFN-alpha A, the percentage of
cases exhibiting inhibition was as follows: melanoma (51.7%), lung cancer
(50%), myeloma (33.4%), ovarian cancer (33.9%), sarcoma (33.3%),
adenocarcinoma of unknown primary (30.4%), breast cancer (28%), acute
leukemia (30.8%), and renal cancer (23%). More marked inhibition (30% of
control or less) was observed in 18.7% of all tumors tested against
IFN-alpha A. Of 60 melanomas tested, 18 (30%) exhibited marked in vitro
inhibition of growth with IFN-alpha A. Although a smaller number of tumors
(71) were tested against IFN- alpha D on a weight basis, it appeared, in
general, to be slightly less active than IFN-alpha A (p less than 0.01),
and only 8% of tumors tested exhibited marked inhibition over the same
dosage range of interferon. Comparison of the dose-response curves for the
68 tumors tested simultaneously against both interferons did not reveal
marked interpatient differences in the inhibition curves, although
IFN-alpha D was slightly less active overall. Tumors exhibiting at least
50% inhibition of tumor colony formation also proved to be sensitive to a
significantly larger number of cytotoxic drugs (tested simultaneously) than
the tumors not inhibited with interferon (p less than 0.0001 for IFN-alpha
A). We conclude that the in vitro clonogenic assay may aid in targeting
tumor types most likely to exhibit interferon sensitivity and assist in
case selection for entry into clinical trials with cloned interferons.
