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Antiproliferative effect of mismatched double-stranded RNA on fresh human tumor cells analyzed in a clonogenic assay
Abstract:
Colony growth in soft agar was used to identify human tumors that were sensitive to the direct antiproliferative effects of mismatched dsRNA (Ampligen). The results suggest that different human solid malignancies vary significantly in their sensitivity to Ampligen. Tumors with 50% or more of their surgical specimens showing sensitivity included carcinoid, glioblastoma, and carcinomas of the kidney, and lung. Resistant tumors (less than 15% sensitivity) included sarcomas and colo-rectal carcinomas. Overall, 42% of the tumor specimens studied showed a 50% or greater reduction in tumor cell colony formation after a single initial treatment with Ampligen (250 micrograms/ml). Interestingly, one patient's tumor which was de novo sensitive to interferon (IFN), but emerged as IFN-resistant following IFN therapy, remained sensitive to Ampligen. Thus, a clonogenic assay may prove useful in identifying human tumors and individuals for clinical trials with Ampligen, including patients resistant to IFN.
Insights
Mismatched double-stranded RNA (dsRNA), known as Ampligen, shows varying effectiveness against human solid tumors. A clonogenic assay can identify Ampligen-sensitive cancers, including those resistant to interferon (IFN).
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Mismatched double-stranded RNA (dsRNA), Ampligen, exhibits direct antiproliferative effects on tumor cells.
- Human solid tumors display heterogeneous responses to novel therapeutic agents.
- Interferon (IFN) therapy can lead to acquired resistance in certain cancers.
Purpose of the Study:
- To evaluate the sensitivity of various human solid tumors to Ampligen using a clonogenic assay.
- To identify specific tumor types that are sensitive or resistant to Ampligen's antiproliferative effects.
- To explore Ampligen's efficacy in tumors that have developed resistance to interferon (IFN).
Main Methods:
- Colony growth in soft agar was employed to assess tumor cell sensitivity to Ampligen.
- Tumor specimens were treated with Ampligen (250 µg/ml) to determine antiproliferative activity.
- Sensitivity was quantified by the reduction in tumor cell colony formation.
Main Results:
- Significant variations in Ampligen sensitivity were observed across different human solid malignancies.
- Sensitive tumors (≥50% sensitivity) included carcinoid, glioblastoma, and kidney and lung carcinomas.
- Resistant tumors (<15% sensitivity) included sarcomas and colorectal carcinomas.
- Overall, 42% of tested tumor specimens showed ≥50% reduction in colony formation after Ampligen treatment.
- One patient's tumor, initially sensitive to IFN but later resistant, remained sensitive to Ampligen.
Conclusions:
- A clonogenic assay is a valuable tool for identifying human tumors and individuals responsive to Ampligen.
- Ampligen demonstrates potential as a therapeutic agent for various solid tumors, including those resistant to IFN.
- Further clinical trials with Ampligen are warranted, particularly for patients with IFN-resistant malignancies.