Method for making reflection defective retroviral vectors for infecting human cells

An ex vivo cell infected with a replication defective recombinant retrovirus which directs the expression of at least one viral or cancer antigen or mutated form thereof in said ex vivo cell, wherein said antigen or mutated form thereof elicits a cell mediated immune response directed to said antigen or mutated form thereof, said viral antigen or mutated form thereof being from a virus pathogenic to humans.

An ex vivo cell infected with a replication defective recombinant retrovirus which directs the expression of a palliative in said ex vivo cell, said palliative being an enzyme not normally expressed in said cell and which converts a purine- or pyrimidine-based prodrug that is non-toxic to said cell to a second agent that is toxic to said cell.

A hybrid env gene for preparing a retrovirus which can selectively carry a gene of interest to a human target cell, the hybrid env gene coding for a hybrid envelope protein comprising:

• (a) a cytoplasmic segment of a first retroviral phenotype;
• and
• (b) a binding segment from a second retroviral phenotype exogenous to the first retroviral phenotype, said second retroviral phenotype being pathogenic to humans, the binding segment selectively binding to said target cell.

A method for producing a replication defective recombinant retrovirus which infects human cells, comprising:

• a) infecting a packaging cell in vitro with a retroviral construct, said packaging cell expressing a gene encoding an envelope protein or mutated form thereof from a virus infectious to humans, said retroviral construct comprising a packaging signal and a gene encoding a protein of interest operably linked to a promoter, said protein of interest being an enzyme not normally found in a human cell and that converts a purine- or pyrimidine-based prodrug that is non-toxic to said human cell into an agent that is cytotoxic to said human cell;
• b) incubating the infected packaging cell of step (a) to allow encapsidation of said retroviral construct by said envelope protein such that a replication defective recombinant retrovirus which infects human cells and which expresses said enzyme therein is produced.