Development of an anticancer therapy using recombinant biˆdobacterium as a new drug delivery system (DDS)

Abstract

Intravenously administered obligate anaerobic bacteria, such as biˆdobacteria, grow speciˆcally in tumor tissues. This speciˆcity is attributed to the following: (1) Vascular walls in tumor tissues have nanometer-to micrometer-wide cracks, which allow the bacteria to pass through; (2) the intratumoral environment is hypoxic, due to poor vasculariza-tion, and therefore biˆdobacteria can survive and proliferate in this anaerobic environment; (3) biˆdobacteria cannot survive in well-oxygenated normal tissues. Moreover, unlike gram-negative bacteria, the gram-positive biˆdobacteria do not produce endotoxins; therefore, there is no risk of endotoxin shock associated with their intravenous administration. Recently, the utility of biˆdobacteria for speciˆc drug delivery to tumor tissues has been highlighted. We have established a novel anti-cancer drug-delivery system using Biˆdobacterium longum for the speciˆc release of anti-tumor antibodies (e.g., antibody-drug complexes or single-chain antibodies) to targeted tumor tissues. Here, we introduce the results of our investigation.