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Related Experiment Videos

Preclinical studies with Ampligen (mismatched double-stranded RNA).

W A Carter, D R Strayer, H R Hubbell

    Journal of Biological Response Modifiers
    |October 1, 1985
    PubMed
    Summary

    Mispairing bases in double-stranded RNA (dsRNA) significantly enhances its therapeutic potential. Ampligen, a novel dsRNA, demonstrates potent anticancer activity with reduced toxicity compared to earlier dsRNAs and interferons.

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    Area of Science:

    • Immunology
    • Pharmacology
    • Biochemistry

    Background:

    • Double-stranded RNA (dsRNA) was historically limited as an anticancer/antiviral therapy due to toxicity and low efficacy of early compounds like polyinosinic-polycytidylic acid (rIn x rCn).
    • Advancements in molecular design offer opportunities to improve the therapeutic index of dsRNA molecules.

    Purpose of the Study:

    • To evaluate the therapeutic potential of a purposefully mispaired dsRNA, Ampligen (rIn x r(C12,U)n), as an anticancer agent.
    • To compare the efficacy and toxicity profile of Ampligen against existing treatments like interferons (IFN) and rIn x rCn.

    Main Methods:

    • In vitro and in vivo studies using various cancer models.
    • Fresh human tumor clonogenic assays to assess sensitivity to Ampligen.
    • Comparative analysis of antitumor activity and toxicity in animal models.

    Main Results:

    • Ampligen exhibited significant antitumor activity across diverse test systems with minimal toxicity.
    • Ampligen demonstrated a broader therapeutic spectrum than interferons.
    • A notable fraction of human solid tumors, resistant to conventional therapies, showed sensitivity to Ampligen.
    • In a renal cancer xenograft model, Ampligen significantly improved survival rates compared to controls and IFN treatment.

    Conclusions:

    • Purposeful base mispairing in dsRNA, exemplified by Ampligen, substantially improves the therapeutic ratio.
    • Ampligen represents a promising anticancer therapeutic with superior efficacy and safety compared to rIn x rCn and IFN.
    • Ampligen's consistent biological and biophysical specifications facilitate its development as a pharmaceutical agent.

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