ONCOLYTIC RNA REPLICONS

摘要

The limited efficacy and/or toxicity of conventional therapies for many types of human cancers underscores the need for development of safe and effective alternative treatments. Towards this goal, the invention describes the direct oncolytic activity of RNA-based vectors derived from poliovirus, termed replicons, which are genetically incapable of producing infectious virus. Replicons of the invention are cytopythic in vivo for human tumor cells originating from brain, breast, lung, ovaries and skin (melanoma). Injection of replicons into established xenograft flank tumors in scid mice resulted in oncolytic activity and extended survival. Inoculation of replicons into established intracranial xenografts tumors in scid mice resulted in tumor infection and extended survival. Histological analysis revealed that replicons infected tumors cells at the site of inoculation and, most importantly, diffused to infect tumor cells which had metastasized from the initial site of implementation. The wide spectrum of cytopathic activity for human tumors combined with effective distribution following in vivo inoculation establishes the therapeutic potential of poliovirus replicons for a variety of cancers.