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Activity of human leukocyte interferon in a human tumor cloning system
Abstract:
Clinical trials using interferon to treat human malignancies are currently hampered by limited supplies of the compound. We have utilized a human tumor cloning system as an assay for the antitumor effects of human leukocyte interferon. Interferon was tested against 62 patients' tumors growing in this soft agar system. A dose-dependent cytotoxic effect of interferon was noted against only five of the patients' tumors. A greater than or equal to 70% decrease in tumor colony-forming units (TCFUs) was noted with one lymphosarcoma cell leukemia, one small cell lung cancer, one adenocarcinoma of the lung, one breast cancer, and a pancreatic cancer. One patient had his tumor cultured in vitro and had a clinical trial with interferon. This patient whose tumor demonstrated in vitro sensitivity had a clinical antitumor effect with interferon therapy. The in vitro results in this study suggest that the human leukocyte interferon currently available has a low level of activity in a human tumor cloning system. Additional testing is needed to determine whether the cloning system can identify the patient(s) who might have an antitumor effect from the interferon.
Insights
Human leukocyte interferon showed limited antitumor activity in a human tumor cloning system, affecting only five of 62 tested malignancies. One patient with an in vitro sensitive tumor experienced clinical benefit, suggesting potential for personalized therapy.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Clinical trials for interferon in human malignancies face limitations due to compound availability.
- A human tumor cloning system offers an assay for evaluating antitumor effects.
Purpose of the Study:
- To assess the in vitro antitumor activity of human leukocyte interferon against a panel of human tumors using a soft agar cloning system.
- To determine if in vitro sensitivity predicts clinical response to interferon therapy.
Main Methods:
- A human tumor cloning system (soft agar assay) was used to test the cytotoxic effects of human leukocyte interferon.
- Interferon was applied to cultures derived from 62 patient tumors.
- One patient with an in vitro sensitive tumor underwent a clinical trial with interferon.
Main Results:
- A dose-dependent cytotoxic effect was observed in only five out of 62 patient tumors.
- Significant reduction (≥70%) in tumor colony-forming units (TCFUs) was noted in lymphosarcoma leukemia, small cell lung cancer, adenocarcinoma of the lung, breast cancer, and pancreatic cancer.
- The patient whose tumor was sensitive in vitro demonstrated a clinical antitumor effect during interferon therapy.
Conclusions:
- Human leukocyte interferon exhibits low in vitro activity in the tested human tumor cloning system.
- The human tumor cloning system may potentially identify patients who could benefit from interferon therapy, warranting further investigation.
- Personalized medicine approaches using in vitro assays could guide interferon treatment decisions.