A short perspective on gene therapy: Clinical experience on gene therapy of gliomablastoma multiforme

Figure 1 Gene transfer can be performed either in vivo or ex vivo. In ex vivo approaches, the cells which are transduced can be autologous or heterologous in origin. In the case of using heterologous cells, cells need to be protected from the recipient’s immune system.

Figure 2 Different gene transfer vectors used in clinical settings (A) and different indications that have been addressed by gene therapy in clinical trials (B). A: By far, adenoviral, retroviral and naked plasmid/DNA have been the most commonly used gene transfer vectors; B: Even though initial studies have been conducted on monogenetic diseases, cancer soon became a major interest, with 65% of all clinical trials to date. The reasons for this are the highly unmet medical need in cancer therapy as well as its big market size. Also, the ethical acceptance of gene therapy as a therapeutic modality is a factor that has supported the shift from monogenetic diseases to cancer.

Figure 3 Sitimagene ceradenovec is an adenoviral vector based suicide gene therapy, which is injected into the wall of the tumor cavity of glioma patients, after the resection of the tumor. Mainly healthy cells will be transduced producing the HSV-tk and converting the pro-drug ganciclovir into ganciclovir monophosphate. The actual cytotoxic metabolite ganciclovir triphosphate is killing possible residual proliferating tumor cells.