HUMAN CLINICAL TRIALS UTILIZING Ad-BASED VECTORS

Currently, Ads are being used in about 22% of all gene therapy clinical trials, with the vast majority of these trials directed toward the treatment of cancer (JGM 2015). Some of the shortcomings of E1-deleted Ad vectors, mainly short-term transgene expression and induction of an immune response, are not of concern in most cancer trials, since the therapeutic is usually only required short term (i.e., once the tumor is gone, the virus is no longer needed). As shown in Table 1.1, clinical trials with Ad vectors follow a trend found throughout the field of gene therapy: many Phase I trials are conducted, few of which progress to Phase II or III. Failure to proceed to a Phase

II or III trial is not usually a result of safety or toxicity issues but, rather, a lack of evidence for efficacy in the Phase I study (although technically Phase I trials are not designed to examine efficacy, almost all clinical researchers look for some measure of efficacy to provide support for Phase II trials). This is a common problem in the gene therapy community, where promising results are obtained in inbred mouse models of the disease, but similar results are not observed in the more diverse human population.