The role of HSV amplicon vectors in cancer gene therapy

Recent progress in tumor biology, virology and immunology has led to new approaches to the gene therapy for cancer. Herpes Simplex Virus (HSV) based vectors are attractive vectors for gene therapy use due to a number of favorable biologic features. Several characterist ics render HSV suitable for gene therapy, including high transduction efficiency, ability to transduce non-dividing cells, high packaging capacity, wide cellular tropism and the ability to package multiple copies of the same gene or several genes. Newer HSV vectors differ in replication potential , sensit ivity to anti-viral agents, neurotoxicity, tumor-specif ic cytotoxicity and persistence in the host cel l . Socalled “oncolytic” HSV based vectors demonstrate selective replication in tumor cells relative to normal tissue. HSV amplicon based vectors allow genetic transfer of multiple transgene copies in the absence of viral genes. This degree of f lexibi l i ty , relat ive to other viral vector systems, has allowed for the use of HSV vectors in a variety of antitumor strategies including oncolytic, as well as immune-based strategies. Successful immune based strategies in animal models have included transfer of cytokines, costimulatory molecules and/or chemokines. Phase I/II clinical trials using HSV based vectors have been initiated.