Historically, it has been assumed that double-stranded (ds) RNAs function at a cellular level exclusively via an interferon (IFN) induction mechanism. However, current studies conducted both in the laboratory and at the clinical level reveal that this assumption is incorrect and, indeed, underestimates the intrinsic antitumor activity of certain dsRNAs. A specific dsRNA (Ampligen) shows strong antiproliferative activity against human carcinoid tumor cells in a clonogenic assay when natural α- and β-IFNs were inactive. Similarly, in vivo studies in which human renal cancer cells were transplanted into athymic mice demonstrate a strong antitumor effect of Ampligen whereas such tumors are largely unaffected by α-IFN treatment. In a comparative study including many fresh human turnors of various histological types (breast, ovarian, melanoma, renal, and carcinoid) numerous examples were uncovered of Ampligen sensitivity (antiproliferative effect) in the face of relative or complete insensitivity to IFNs. Synergistic effects of Ampligen plus IFN overcame the resistance of some human tumor cells to either biological modifier given alone. It can also be demonstrated that the antitumor action of Ampligen on certain human lung tumor cells is not shared by polyinosinic polycytidylic acid, thus indicating that different dsRNAs may themselves exhibit dissimilar effects on various human tumors.
Received June 11, 1985; accepted June 11, 1985.
Address correspondence and reprint requests to Dr. W. A. Carter at Institute for Cancer and Blood Diseases, Hahnemann University, Broad and Vine Streets, Philadelphia, PA 19102, U.S.A.
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