Conditionally replicating herpes vectors for cancer therapy

The use of genetically engineered viral vectors for tumor therapy initially involved replication-defective vectors, generally derived from retro- or adenoviruses, for the transfer of genes to cause tumor growth inhibition or tumor destruction. However, because of limitations involving vector delivery and relatively low levels of gene transfer, such vectors systems have proven relatively inefficient for the treatment of large solid tumors. In an attempt to overcome this problem, vectors have been developed that can replicate within the tumor and thus increase the efficiency of tumor cell destruction, but appropriate tumor targeting has been a major challenge for such systems. Vectors are needed that replicate within tumor cells and cause tumor cell destruction but that cause no local or systemic toxicity, because they fail to grow within normal tissues. Studies that I and my colleagues performed initially focused on the treatment of malignant brain tumors using local vector delivery to avoid damaging normal brain and associated tissues. We and others have since expanded the scope of this project to target cancers in the nervous system and elsewhere, using targeted or systemically delivered vectors derived from herpes simplex virus-1 (HSV-1) .