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.