Abstract
Recent development of molecular targeting drugs against cancer is remarkable and attractive. On one hand, the population of cancer cells is heterogeneous due to the phenotypic instability of cancer cells, resulting in the appearance of drug-resistant and metastatic cells. Thus, the complete suppression of cancer is still difficult, and the troublesome situation is similar to hitherto chemotherapy. Therefore, it seems to be necessary to seek for targets in microenvironment of cancer tissues rather molecular targets in cancer cells, leading to attack whole cancer tissues like a surgery. We are developing Drug Delivery and Production System (DDPS) to selectively deliver and/or produce a large amount of anticancer drugs at a lesion part, directing attention to characteristic hypoxia in the solid cancer. As the delivery tool and micro production plant, we used non-pathogenic and anaerobic bifidobacteria. We established recombinant bifidobacteria expressing cytosine deaminase (CD) that coverts 5FC(low-toxic pro-drug) to 5FU.When tumor-bearing animals were treated by iv injecting the recombinant bacteria with CD followed by po 5FC administration, suppression of tumor growth was observed without any side effects. Although our cancer treatment system with Bifidobacterium has been criticized with a priori sense that iv injection of bacteria is dangerous, various biological tests indicated the safety of our cancer treatment system with Bifidobacterium, leading to the clinical phase 1 test.
