Cancer Gene Therapy Clinical Trials. From the Bench to the Clinic

This chapter focuses on some of the most important considerations in the design of gene therapy trials. Gene therapy is a medical intervention based on the introduction of genetic material in human cells in vivo or in vitro. Preclinical studies in support of use of gene transfer vector in clinical studies should be conducted in compliance with the regulations for good laboratory practice. It is suggested that when determining a phase II dose during a phase I gene therapy study, the aim should be to identify the dose that can achieve the maximum biologic effect, which can occasionally reach a plateau at doses below the maximum tolerated dose. In gene transfer trials, it is essential that meaningful correlative endpoints are employed in order to correlate the employed doses with biological effect and select the most appropriate dose for phase II setting. This usually requires repeat tumor biopsies, a task not always easy when performed in a multicenter setting or for deep-seated tumors. It is found that despite systematic efforts in most gene therapy trials to assess the distribution of viral vectors/transgenes by performing repeat tissue biopsies, the results are often suboptimal. It is suggested to characterize the immune response against the vector and/or transgene if applicable, which certainly can affect the effectiveness of treatment, especially after systemic administration of the viral agent.