The 17th Annual Meeting 2011 Japan Society of Gene Therapy

Abstract

Cancer treatment has been improved by recent progress in multimodal treatments. However, only palliative therapies remain for patients who have disease that is refractory to standard therapies including surgery, chemotherapy, or radiotherapy. The development of novel therapies is an urgent social need for such refractory cases. Gene therapy has been considered to be one of the so-called fourth therapies for cancer treatment. Although several approaches have shown some benefit, their clinical efficacies have generally been insufficient and unpredictable. The development of a new strategy to induce and maintain antitumor effects for longer periods in predictable way is imminent. To establish a new generation of antitumor therapies, we conducted several phase I clinical studies of immune and cell therapies targeting metastatic solid tumors. Our first phase I study involved immune gene therapy using a GM-CSF gene-transduced autologous tumor vaccine for stage IV renal cell cancer. Our results showed that this new immune gene therapy was safe and induced tumor-specific immune reactions in patients. Two out of four patients survived for more than six years. However, the clinical antitumor effect, i.e., reducing the size of large tumor masses, was inadequate with this approach alone. To overcome this limitation, we next used a mouse tumor model to explore several combination therapies for enhancing GM-CSF gene therapy. Our results demonstrated the effectiveness of the combined use of the TARC and RANTES chemokine genes with the GM-CSF gene. In the clinical setting, we adopted new cell therapy methods, using tumor associated antigen (TAA)pulsed dendritic cells with cytotoxic T cells, involving the breakage of immune tolerance and the induction of TAA-specific immune responses. This phase I clinical trial is now underway and thus far no severe adverse events have been observed. The combination of GM-CSF gene therapy followed by novel immune cell therapy may be our next challenge. Our second gene therapy approach is oncolytic virotherapy, with current targets of measles virus and enterovirus. Our mouse tumor model studies demonstrated that both viruses would be promising candidates. Collectively, we hope that both immune gene therapy and virotherapy will cast a new light on the field of clinical cancer treatment in near future.Special Lecture I Viruses as Allies of Man: From Swords to PloughsharesInder Verma Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037-1002, USA At the beginning of the third millennium, man has an opportunity to fulfill the cherished goal of improving the lot of humankind. Newer modalities of medicine are being practiced and daily new breakthroughs are being reported. I would like to talk about gene therapy, a form of molecular medicine, which will have a major impact on human health. At present, gene therapy is being contemplated for both genetic and acquired diseases. These include hemophilia, cystic fibrosis, diabetes, canc...