Laboratory of Pharmaceutics and Biopharmaceutics

• Fundamental studies for gene delivery system using viral vectors
• Vaccine therapy against newly formed blood vessel
• Drug delivery system using anti-tumor vessel antibodies

Gene delivery

The rapidly changing field of gene therapy promises a number of innovative treatments for cancer patients. Advances in genetic modification of cancer and immune cells have led to numerous clinical trials for cancer therapy. However, there is at present that cancer gene therapy is not sufficient therapeutic effect can be obtained. Successful cancer gene therapy depends largely on innovative delivery systems that can efficiently deliver the therapeutic genes or produced-proteins into the target tissues and cells.
Recombinant adenovirus (Ad) vectors continue to be the preferred vectors for cancer gene therapy because they can efficiently transfer genes into cancer cells. However, there is a limitation such as the coxsackievirus-adenovirus receptor (CAR)-dependent gene transfer. We develop the several types of fiber-modified Ad vectors. Fiber-modified Ad vectors can be effective in overcoming the limitations of conventional Ad vectors, specifically their inefficient gene transfer into cells lacking the CAR. In addition, fiber-modified Ad vectors can efficiently transfer genes into CAR negative cancer cells in vivo.
We are going to develop next generation of gene vectors or delivery system of transfer gene produced-proteins that have become promising tools for cancer gene therapy.

Vaccine therapy and DDS

There are surgical treatment, radiotherapy, and chemotherapy in the treatment for cancer therapy. The immune therapy is expected as a novel cancer therapy that has a low side effect. In tumor tissue, new blood vessels provide expanding tissues and organs with oxygen and nutrients, and remove the metabolic waste. We hypothesized that vaccination with tumor-induced endothelial cell (TEC), which composes tumor vessel would induce an autoimmune response targeting tumor angiogenesis. The immune therapy targeting TEC is more effective than that one targeting tumor cell, because a number of tumor cells rely on a TEC. In this study, we show that immunotherapy of solid tumor using dendritic cells(DC) pulsed with TEC inhibits tumor growth and angiogenesis in tumor bearing mice. Furthermore, we develop the antibody to the tumor blood vessel by the phage displaymethod. The rheumatoid pannus, the site of inflammation and joint destruction in therheumatoid synovium, relies on the development of angiogenesis to sustain its growth. Obesity is the main etiology of metabolic syndrome and characterized by increase of adipose tissue due to excessive caloric intake. In obesity, angiogenesis is also essential for the growth of adipose tissue. Our studies show that the immunotherapy against neovascular endothelial cells in adipose tissue and in rheumatoid pannus may provide novel approach for obesity and rheumatoid arthritis. We also developed anti-tumor vessel antibodies using phage display technique for tumor targeting.