Synergistic antiproliferative effect of human interferons in combination with mismatched double-stranded RNA on human
Abstract:
Four human tumor cell lines were studied for their response to antiproliferative effects of various interferons (IFNs) alone and in combination with the novel mismatched dsRNA, r(I)n r(C12,U)n (Ampligen). RT4 cells (bladder carcinoma) were resistant to Ampligen alone, while A2182 (lung carcinoma), HT 1080 C14 (fibrosarcoma) and RT112 (bladder carcinoma) cells were inhibited in a dose-dependent manner. In contrast, RT4 cells were sensitive to the antitumor effects of IFNs as were HT1080 C14 and RT112 cells, while A2182 cells were resistant. In 3 of 4 cell lines, the recombinant IFNs were less effective than the corresponding natural IFNs when compared by analysis of variance on an IRU/ml basis over a range of concentrations. In all cell lines, a synergistic antiproliferative effect was seen with all IFN preparations studied in combination with Ampligen, as calculated by the isobole method according to Berenbaum (1981). The antiproliferative effect of IFN was potentiated greater than 3.3- to greater than 250-fold, depending on the cell lines, IFN, and concentrations used. Varying the concentration of beta ser-IFN while holding the Ampligen concentration constant gave synergy at all of the physiologically achievable concentrations tested in RT4 cells. These results indicate that: Ampligen worked synergistically with all IFNs in all cell lines studied; growth inhibition of cells resistant to IFNs can be potentiated by low doses of Ampligen; the antiproliferative effect of IFNs can be potentiated by Ampligen in Ampligen-resistant cells; and Ampligen may work by a mechanism other than, or in addition to, the induction of IFNs.
Insights
Ampligen, a novel dsRNA, demonstrated synergistic antiproliferative effects when combined with interferons (IFNs) across various human tumor cell lines. This combination therapy enhanced IFN efficacy, even in cells resistant to IFNs alone, suggesting Ampligen may have additional mechanisms of action.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Interferons (IFNs) are crucial in cancer therapy.
- Ampligen (r(I)n r(C12,U)n) is a novel mismatched dsRNA with potential antiproliferative properties.
- Tumor cell line responses to IFNs and Ampligen vary.
Purpose of the Study:
- To investigate the combined antiproliferative effects of IFNs and Ampligen on human tumor cell lines.
- To determine if Ampligen can potentiate the efficacy of IFNs, particularly in IFN-resistant cells.
- To explore potential mechanisms of action for Ampligen in combination therapy.
Main Methods:
- Testing antiproliferative effects of IFNs and Ampligen alone and in combination on four human tumor cell lines (RT4, A2182, HT 1080 C14, RT112).
- Dose-response studies and analysis of variance were used to compare natural and recombinant IFNs.
- Synergistic effects were quantified using the isobole method (Berenbaum, 1981).
Main Results:
- Ampligen showed dose-dependent inhibition in three of four cell lines, while RT4 cells were resistant.
- IFNs were effective against RT4, HT1080 C14, and RT112 cells but not A2182 cells.
- A significant synergistic antiproliferative effect was observed with all IFN-Ampligen combinations.
- Ampligen potentiated IFN effects by 3.3- to over 250-fold, enhancing efficacy in IFN-resistant cells.
- Natural IFNs were generally more effective than recombinant IFNs.
Conclusions:
- Ampligen synergizes with all tested IFNs across all cell lines.
- Ampligen can potentiate IFN-mediated growth inhibition in cells resistant to IFNs.
- Ampligen may exert its effects through mechanisms beyond IFN induction.
- Combination therapy with Ampligen and IFNs holds promise for cancer treatment.
Related Concept Videos
Experimental RNAi
Abnormal Proliferation
Targeted Cancer Therapies
There are several types of targeted therapies against specific...
Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
Tumor Immunotherapy
Inhibitors of Viral Protein Synthesis


