Viral vector directed to predetermined target cells

#1. Field of the Invention

#The invention is related to the fields of viral vectors for targeted gene therapy and pharmaceutical preparations, and more particularly to viral vectors for tumor therapy.

#2. Description of the Related Art

#For a detailed description of a preferred embodiment of the invention, reference will now be made to the accompanying drawings wherein:

#FIG. 1A. is a schematic representation of the structure of wild type SV5, with a native HN protein that functions as a receptor binding protein and an F protein or fusion protein. This virion has little cell type specificity. The concentric circles represent the virion lipid envelope and the squiggle represents the viral genome.

#FIG. 1B. is a schematic representation of an SV5 that does not express HN (HN.sub.minus). This virion does not have a cell recognition protein.

#Viruses and virus-based vectors represent a powerful tool for the delivery of recombinant molecules to cells. A major drawback to current systems has been the inability to target and limit an infection by a recombinant virus to predetermined cell types or tissue. As disclosed herein the recombinant SV5 vectors can target and limit an infection to a predetermined population of cells.

#An embodiment of the present invention utilizes the paramyxovirus, simian virus 5 (SV5), a common and non-pathogenic RNA virus. SV5 contains two viral glycoproteins in its envelope: the HN protein which functions in attachment to host cell receptors, and the F protein which fuses the virion envelope with the target cell plasma membrane. SV5 is engineered to encode a foreign glycoprotein in place of the normal viral attachment protein HN. Virions containing the foreign membrane protein in the viral envelope are then tested for their cell-type specificity, which is limited to cells expressing the ligand that is complementary to the virion-associated foreign protein or glycoprotein. SV5 is preferred for this virus gene delivery system, because the SV5 F protein is the only known paramyxovirus fusion protein which has been shown to act independently of its homologous HN attachment protein.

#In one embodiment of the present invention, the cell-type specificity of an SV5 infection is predetermined by incorporating the appropriate foreign membrane protein into the viral envelope. In an example of this invention, recombinant SV5 (rSV5) is engineered to incorporate a membrane-bound form of a single chain antibody (sFv) into its envelope. The specificity of infection by this rSV5 is thus limited to cells expressing the appropriate surface antigen that is recognized by this antibody. This aspect of the disclosed compositions and methods affords a high degree of flexibility in choice of cell types to be targeted by the SV5 vectors. An example of this embodiment is virions that contain in their envelope an sFv to HER2, a cell surface antigen that is overexpressed in a large number of carcinomas. For example, HER2 is a cell surface membrane protein which is overexpressed in very large percentage (.about.25%) of human lung, breast, ovary and stomach carcinomas and expression levels correlate with the aggressiveness of malignancy (Salmon et al., 1989).