Title : In situ delivery and production system of anti-cancer molecules with gene-engineered bifidobacterium
Abstract:
Regardless of recent rapid progresses in cancer therapy by molecular-targeting and regulating immune check points, the side effects of those treatments are still troublesome for the patients to be overcome. We have developed an in situ Drug Delivery and Production System(iDPS) with non-pathogenic anaerobic Bifidobacterium to target hypoxia in cancer tissues. Hypoxic microenvironment is well known to be a causative factor of tumor cell resistance to radiation therapy and chemotherapy, and also recognized as a condition for malignant progression of cancer cells. When the recombinant Bifidobacteria carrying genes of anticancer products were iv administered, they rapidly disappeared from normal tissues within a few days, and proliferated to produce anti-cancer products selectively in tumor tissues. Administration of bacteria into blood vessels, even if non-pathogenic, may be considered dangerous in that it may induce sepsis, however, our system is not the case. Recently, articles on the effects of cancer treatment with bacteria appeared and brought to light the potential utility of bacteria in cancer treatment. One of our recombinant bacterial clones, which expresses cytosine deaminase converting 5FC (low toxic prodrug of 5FU) to 5FU, is now underway of clinical trial (Phase 1/2) sponsored by AnaeroPharma Science, Inc., a venture company originated from Shinshu University. Additionally, several clones to produce anti-cancer molecules for iDPS, such as anti-HER2 scFv, anti-immune check point scFvs, antitumor cytokines, have been being established. We will discuss the safety and rationale of iDPS by referring to our experimental data.
Audience take away:
• It is rationale to target anaerobic condition of cancer microenvironment. The audience can direct their attention to the specificity of cancer tissues, such as hypoxia, rather than cell-specific molecules of cancer, to develop a new anticancer drug.
• We believe that our work help the audience to learn a new idea free from conventional senses.
• Yes, in terms of idea but not concrete techniques.
• I think that even if any sophisticated cancer cell specific drug is developed, resistant cells to the drug will appear soon, because cancer population is heterogeneous. Taking the situation into consideration, it seems to be more effective to deliver a large amount of any toxic molecules selectively to tumor tissues by making use of macroscopic specificity, hypoxia, to overcome problems derived from cellular heterogeneity.
• Our iDPS is able to produce anticancer molecules continuously, so that it may contribute to lower the drug price in the future. We think that bacteria can be regarded as proliferative liposomes.
