Gene therapy for the treatment of solid tumors using recombinant adeno-associated virus vectors

An adeno-associated virus (AAV) vector, comprising:

• a first gene, comprising a drug susceptibility gene;
• and
• a second gene comprising a tumor suppressor gene, wherein the first gene and the second gene are operably linked to control elements capable of directing the in vivo transcription and translation thereof.

An adeno-associated virus (AAV) vector, comprising a beta interferon (IFN-β) gene and control elements operably linked thereto, wherein said control elements are capable of directing the transcription and translation of the gene in a host cell.

A method of simultaneously delivering a first and a second gene to a target solid tumor cell, comprising:

• (a) providing a recombinant adeno-associated virus virion (rAAV virion) which comprises a first gene capable of being expressed to provide the target cell with enhanced susceptibility to a selected cytotoxic agent and a second gene capable of providing an ancillary therapeutic effect, wherein said first gene and said second gene are operably linked to control elements capable of directing the in vivo transcription and translation thereof;
• and
• (b) transducing the target solid tumor cell with the rAAV virion.

A solid tumor cell transduced with a recombinant adeno-associated virus virion (rAAV virion) which comprises an AAV vector, said AAV vector including a first gene capable of being expressed to provide the tumor cell with enhanced susceptibility to a selected cytotoxic agent, a second gene capable of providing an ancillary therapeutic effect, and control elements operably linked to the first gene and the second gene, wherein said control elements are capable of directing the in vivo transcription and translation of the first gene and the second gene.

A method of treating neoplastic disease in a mammalian subject, comprising:

• (a) transducing a solid tumor cell of said subject in vivo using a therapeutically effective amount of a pharmaceutical composition which comprises (i) a pharmaceutically acceptable excipient, and (ii) recombinant adeno-associated virus virions (rAAV virions), wherein said rAAV virions comprise an AAV vector having a first gene capable of being expressed to provide the transduced tumor cell with enhanced susceptibility to a selected cytotoxic agent, a second gene capable of providing an ancillary therapeutic effect, and control elements operably linked to the first gene and the second gene, wherein said control elements are capable of directing the in vivo transcription and translation of the first gene and the second gene when present in the mammalian subject;
• and
• (b) administering a therapeutically effective amount of the selected cytotoxic agent to the mammalian subject.

A method of treating neoplastic disease in a mammalian subject, comprising transducing a solid tumor cell of said subject in vivo using a therapeutically effective amount of a pharmaceutical composition which comprises:

• (a) a pharmaceutically acceptable excipient;
• and
• (b) a recombinant adeno-associated virus virion (rAAV virion) comprising an AAV vector that contains a gene capable of being expressed by the transduced cell to provide either a tumorstatic or an immunogenic effect, and control elements operably linked to the gene, wherein said control elements are capable of directing the in vivo transcription and translation of the gene when present in the mammalian subject.

A composition, comprising:

• (a) a pharmaceutically acceptable excipient;
• and
• (b) a recombinant adeno-associated virus virion (rAAV virion), wherein said rAAV virion comprises an AAV vector having (i) a first gene comprising a drug susceptibility gene, (ii) a second gene capable of being expressed to provide an ancillary therapeutic effect, and (iii) control elements capable of directing the in vivo transcription and translation of the first and second genes, wherein the first and second genes are operably linked to said control elements.

A composition, comprising:

• (a) a pharmaceutically acceptable excipient;
• and
• (b) a recombinant adeno-associated virus virion (rAAV virion), wherein said rAAV virion comprises an AAV vector having a beta interferon (IFN-β) gene and control elements operably linked thereto, wherein said control elements are capable of directing the transcription and translation of the gene in a host cell.