Treatment of cancer using TLR3 agonists
Document Type and Number:
United States Patent 8409813
The present invention relates generally to the fields of genetics and medicine. More specifically, the present invention relates to improved methods of treating cancers using a TLR3 agonist, by assessing the expression of a TLR3 receptor by cancer cells.
Generally, the polynucleotides need to be resistant to nucleases in order to remain as macromolecules for a sufficient length of time; polynucleotides are less sensitive to nuclease attack when they are in a helical complex. However, certain analogs such as Ampligen appear to retain their TLR3 agonist activity.
One example of a TLR3 agonist is Ampligen (Hemispherx, Inc., of Rockville, Md., U.S.A.), a dsRNA formed by complexes of polyriboinosinic and polyribocytidylic/uridylic acid, such as rIn:r(CX,U or G)n where x has a value from 4 to 29, e.g., rIn:r(C12 U)n. Many mismatched dsRNA polymers which behave similarly to Ampligen have been studied; mismatched dsRNA based on poly I:C have included complexes of a polyinosinate and a polycytidylate containing a proportion of uracil bases or guanidine bases, e.g., from 1 in 5 to 1 in 30 such bases. The key therapeutic advantage of mismatched dsRNAs over other forms of natural and/or synthetic dsRNAs is a reported reduction in toxicity over compounds such as those described in Lampson et al. in U.S. Pat. No. 3,666,646.
Ampligen is of a polyI/polyC compound (or a variant thereof comprising a polyI/polyC12U RNA molecule). Ampligen is disclosed for instance in EP 281 380 or EP 113 162. Ampligen has been proposed for the treatment of cancer, viral infections and immune disorders. It was developed primarily for the potential treatment of myalgic encephalomyelitis (ME, or chronic fatigue syndrome/chronic fatigue immune dysfunction syndrome, CFS/CFIDS). Less