Patent ID: 6824771
Filing Date: 2004-11-30
Classification: A61K,C12N

Abstract:
A method for reducing tumor burden in a subject in need thereof comprising administering to the subject in need thereof a therapeutically effective amount of a modified conditionally replicative adenovirus;said modified conditionally replicative adenovirus having greater infectivity in tumor cells than wild-type adenovirus, and hence is modified, by: the modified conditionally replicative adenovirus having a modified fiber protein containing a ligand, by the conditionally replicative adenovirus containing and expressing a nucleotide sequence encoding the ligand, and wherein the ligand comprises Arg-Gly-Asp in the HI loop of the fiber; or the modified conditionally repticative adenovirus containing a fiber knob domain from a different subtype of adenovirus; whereby the ligand or fiber knob domain provides a pathway to cell binding by the modified conditionally replicative adenovirus other than the coxsackie-adenovirus receptor, and thereby enhances infectivity of the conditionally replicative adenovirus in tumor cells over that of wild-type adenovirus, and wherein the modified conditionally replicative adenovirus contains a deletion of nucleotide sequences encoding the E1b-55K protein, or the RB binding site of E1a, such that the replicating adenovirus infects the tumor cells, and thereby reduces tumor burden in the subject.