Retroviral Vectors for Cancer Gene Therapy

Intragene Sciences, Inc., San Marino CA

Investigators

Abstract

Many strategies for gene therapy of solid tumors such as prostate cancer have involved the use of Moloney murine leukemia (MLV)-based retroviral vectors, but gene transfer with standard replication-defective MLV vectors has not been efficient due to their low titers and limited diffusion into the tumor. Gene transfer using replication-competent retroviral vectors would be more efficient, as each successfully transduced tumor cell would itself become a virus-producing cell. We have devised a novel replication-competent MLV vector that has proven to be stable over at least 8 serial passages in cell culture, and is capable of highly-efficient gene delivery to solid tumors in vivo in a nude mouse xenograft model. Until now, the use of such replication-competent virus vectors has rarely been contemplated due to the risks associated with uncontrolled spread of replication-competent virus. We now propose to target these vectors specifically to prostate tumors by engineering the prostate-specific probasin promoter into the retroviral long terminal (LTR) to control transcription of the replication-competent retroviral RNA genome. Targeting the retrovirus specifically and exclusively to tumor cells would limit and control the replicative process and minimize the risk to normal cells, and would represent a significant improvement in vector design. PROPOSED COMMERCIAL APPLICATIONS: Targeted delivery of therapeutic genes for cancer treatment or gene replacement therapy.