Antiproliferative effects of interleukin-12 treatment on human tumor colony-forming units taken directly from patients.
Interleukin-12 (IL-12) has important immunomodulatory effects on T and natural killer (NK) cells that might be exploited in anticancer treatment. Murine IL-12 models have shown antimetastatic and antitumor effects against murine tumors in vivo. Data on the effects of human IL-12 on human tumors are confined to 51Cr-release assay studies showing that IL-12 increases NK activity against cancer cells. We used a human tumor cloning assay (HTCA) to investigate the effects of human IL-12 on solid tumors taken directly from patients. The HTCA is suitable to test direct, as well as immune-mediated, antitumor effects of cytokines on heterogeneous cell preparations derived from fresh tumors. Single cell suspensions prepared from 193 tumors were continuously exposed (14 days) to 10, 100 and 1000 ng/ml of human IL-12 in a capillary HTCA. Seventy-four (38%) specimens were evaluable. Inhibition of tumor growth was observed in 35 specimens (47%; concentration-related in 33 cases), including cancers of the ovary, lung, prostate, breast, colon and kidney, as well as melanoma. Antitumor effect was observed in 10 (14%), 18 (24%) and 32 (43%) tumors, at 10, 100 and 1000 ng/ml of IL-12, respectively. One specimen (1%), a melanoma, showed stimulation of tumor proliferation only at 100 mg/ml of IL-12. Our results show that IL-12 has substantial in vitro activity against a variety of solid tumors taken directly from patients. Clinical trials of IL-12 in patients with solid tumors are warranted.
Izquierdo
M A
MA
Institute for Drug Development, Cancer Therapy and Research Centre, San Antonio, TX 78229, USA.
Degen
D
D
Sypek
J P
JP
Von Hoff
D D
DD
D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D011994:Recombinant Proteins; D018664:Interleukin-12