Delivery systems intended for in vivo gene therapy of cancer: targeting and replication competent viral vectors

Cancer gene therapy represents one of the most rapidly evolving areas in pr e-clinical and clinical cancer research. Application of gene transfer techn iques in clinical trials has made increasingly obvious that several issues will need to be addressed prior to meaningful incorporation of gene therapy in the care of cancer patients. Two of the most important problems to over come are lack of selectivity of the existing vectors and low efficiency of gene transfer. This review focuses on use of targeting and replication comp etent vectors in order to overcome these obstacles. Targeted gene therapy o f malignancies call be achieved through vector targeting or transcriptional targeting and can improve the therapeutic index of gene transfer by preven ting damage of normal tissues, an important requirement if systemic gene de livery is contemplated. Replication competent: viral vectors can improve th e efficiency of gene transfer. Provisionally replicating viruses can also i mprove the therapeutic index by targeting toxicity to tumor cells. A variet y of provisionally replicating viruses, such as the attenuated adenovirus O NYX-015, the adenovirus CN706 that selectively replicates in prostate cance r cells, the double mutant herpes simplex virus G207, the human reovirus, a nd the Newcastle disease virus are currently in clinical trials. Early clin ical results and limitations in the application of these vectors are discus sed. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.