9th ESOU: Gene therapy shows promise in non-muscle invasive bladder cancer

Gene therapy shows promise in the treatment of non muscle invasive bladder cancer with current trials indicating that the gene therapy approach might offer less toxic side effects, according to Prof. Seth Lerner who spoke on the subject during the 9th EAU Section of Oncological Urology (ESOU) Meeting held this weekend in Hamburg, Germany.

Saying that non-muscle invasive urothelial bladder cancer (NMIBC) has a high recurrence rate and no new drug approvals in recent years, Lerner said there is a need to consider other treatment options aside from chemotherapy and targeted therapeutics.

Moreover, he said that NMIBC is the most expensive cancer from diagnosis until death and is linked with a long-term progression rate of 30 to 40% despite high initial response rates to induction BCG with maintenance. Among the emerging therapies is gene therapy, which Lerner said have attracted several extensive studies in recent years.

“Bladder cancer is an ideal target for gene therapy due to the ease of access to tumors with opportunities for intravesical therapy as well as direct tumor injection,” he said. In gene therapy a vector or “delivery module” is required and two current methods are the so-called viral and non-viral mediated gene delivery.

Lerner explained that the most common viral method used in human bladder cancer trial to date is adenovirus, which are double-stranded DNA viruses with comparatively large carrying capacity but lacking the capability of integration seen in retroviruses. The adenovirus basically does its work by maintaining the genes responsible for replication as a tool for killing cancer cells.

Gene therapy’s effects are achieved through gene augmentation or gene blocking, and Lerner noted that there are a number of gene therapies that have been developed such as corrective, immunomodulatory, suicide and complementary gene therapy.

Lerner, a urology professor at Baylor College of Medicine in Houston, Texas in the US said that his laboratory team has focused on adenoviral mediated suicide gene therapy based on the transduction of replication deficient adenovirus that contains the herpes simplex virus (HSV) type 1 thymidine kinase (TK) in combination with the pro-drug acyclovir (GCV).

“Why gene therapy?” Lerner asked, noting that gene therapy is one of the most advanced new biomedicine treatment strategies, and that technological hurdles have been cleared. He also added that current clinical studies are robust and that there are extensive pre-clinical and clinical experiences.

He also deflected criticisms on gene therapy particularly a peer review article which said that there is a lack of progress in gene therapy studies, specifically “the inability to enhance viral vectors to better infect the urethelium…”

As rebuttal, Lerner said: “Viral and non-viral mediated gene delivery appears to be a highly relevant strategy for both intravesical and systemic delivery of therapeutic ablative therapy and immunotherapy. Several Phase 2 trails are underway based on the safety and potential efficacy demonstrated in Phase 1 trials.”