Cytopathic viruses for therapy and prophylaxis of neoplasia
AssigneeOnyx Pharmaceuticals, Inc.
InventorFrancis McCormick
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Abstract
Methods and compositions for treating neoplastic conditions by viral-based therapy are provided. Mutant virus lacking viral proteins which bind and/or inactivate p53 or RB are administered to a patient having a neoplasm which comprises cells lacking p53 and/or RB function. The mutant virus is able to substantially produce a replication phenotype in neoplastic cells but is substantially unable to produce a replication phenotype in non-replicating, non-neoplastic cells having essentially normal p53 and/or RB function. The preferential generation of replication phenotype in neoplastic cells results in a preferential killing of the neoplastic cells, either directly or by expression of a cytotoxic gene in cells expressing a viral replication phenotype.
Claims4
A method for ablating neoplastic cells in a cell population, comprising the steps of:
- contacting under infective conditions (1) a recombinant replication deficient adenovirus substantially lacking an expressed viral oncoprotein capable of binding a functional Rb tumor suppressor gene product, said viral oncoprotein being an adenovirus E1a polypeptide lacking a functional CR1 domain that binds p300 as shown in FIG. 1, with (2) a cell population comprising non-neoplastic cells containing said functional Rb tumor suppressor gene product capable of forming a bound complex with a viral oncoprotein and neoplastic cells lacking said functional Rb tumor suppressor gene product, thereby generating an infected cell population and ablating neoplastic cells.
Dependencies are inferred from the claim text.