Viruses are the most commonly used vectors for clinical gene therapy. The risk of dissemination of a viral vector into the environment via excreta from the treated patient, a phenomenon called shedding, is a major safety concern for the environment. Despite the significant number of clinical gene therapy trials that have been conducted worldwide, there is currently no overview of actual shedding data available. In this article, an inventory of shedding data obtained from a total of 100 publications on clinical gene therapy trials using retroviral, adenoviral, adeno-associated viral and pox viral vectors is presented. In addition, the experimental set-up for shedding analysis including the assays used and biological materials tested is summarized. The collected data based on the analysis of 1619 patients in total demonstrate that shedding of these vectors occurs in practice, mainly determined by the type of vector and the route of vector administration. Due to the use of non-quantitative assays, the lack of information on assay sensitivity in most publications, and the fact that assay sensitivity is expressed in various ways, general conclusions cannot be made as to the level of vector shedding. The evaluation of the potential impact and consequences of the observations is complicated by the high degree of variety in the experimental design of shedding analysis between trials. This inventory can be supportive to clinical gene therapy investigators for the establishment of an evidence-based risk assessment to be included in a clinical protocol application, as well as to national regulatory authorities for the ongoing development of regulatory guidelines regarding gene therapy.

The treatment of superficial bladder cancer requires adjuvant therapies besides transurethral resection because of a high recurrence rate after this standard treatment alone. Current adjuvant therapies involve intravesical chemotherapy for patients at low and intermediate risk for recurrence and progression, and intravesical bacillus Calmette-Guérin for patients at intermediate and high risk. However, these adjuvant therapies fail in a significant number of patients, dictating the need for new and improved adjuvant treatment modalities for superficial bladder cancer. Immunotherapy aiming at the modulation of the immune system of the patient is a promising alternative adjuvant. This review discusses the current status of the clinical development of various immunotherapy approaches for superficial bladder cancer, including passive immunotherapy, immune stimulants, immunogene therapy and cancer vaccination.

From the present study we conclude that a significant association between AA and AA metabolites in serum and PCa progression exists, although serum concentrations of HETEs exhibited low sensitivity toward the diagnosis of PCa.

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