Comparative studies of ampligen (mismatched double-stranded RNA) and interferons.
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 alpha- and beta-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 alpha-IFN treatment. In a comparative study including many fresh human tumors 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.
W A
WA
Carter
H R
HR
Hubbell
L J
LJ
Krueger
D R
DR
Strayer
D000818:Animals; D000970:Antineoplastic Agents; D018288:Carcinoma, Small Cell / Q000628:therapy; D004351:Drug Resistance; D004357:Drug Synergism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007372:Interferons / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000628:therapy; D008175:Lung Neoplasms / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000628:therapy*; D011070:Poly I-C / Q000494:pharmacology; D011072:Poly U; D011131:Polyribonucleotides / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay; D001749:Urinary Bladder Neoplasms / Q000628:therapy
D000970:Antineoplastic Agents; D011131:Polyribonucleotides; D011072:Poly U; D007372:Interferons; C047490:poly(I).poly(c12,U); D011070:Poly I-C