Our laboratory has developed a novel delivery platform using an attenuated non-toxic and non-pathogenic bacterium Listeria monocytogenes that infects
tumor cells and selectively survives and multiplies in
metastases and primary
tumors with help of myeloid-derived suppressor cells (MDSC) and immune suppression in the tumor microenvironment (TME). 32P was efficiently incorporated into the Listeria bacteria by
starvation of the bacteria in saline, and then cultured in
phosphorus-free medium complemented with 32P as a nutrient. Listeria-32P kills
tumor cells through both 32P-induced ionizing radiation and Listeria-induced
reactive oxygen species (ROS). The levels of 32P and Listeria were studied in various normal and
tumor tissues, at sequential time points after injection of mice with
pancreatic cancer (syngeneic model Panc-02). We found that 32P and Listeria predominantly accumulated in
tumors and
metastases, with their highest accumulation 4 hrs (32P) and 3 days (Listeria) after injection. Listeria also penetrated the transgenic KPC (conditionally express endogenous Kras-G12D and p53-R172H mutant alleles) pancreatic
tumors and
metastases. This is remarkable since KPC
tumors, like human
tumors, exhibit a stromal barrier, which prevents most drugs from penetrating the pancreatic
tumors. Therapeutic treatment with Listeria -32P resulted in a strong reduction of the growth of
pancreatic cancer at early and late stages in Panc-02 and KPC mice. These results highlight the power of Listeria as new delivery platform of
anticancer agents to the TME. Not only were therapeutic levels of radioactive Listeria reached in
tumors and
metastases but the selective delivery also led to minimal side effects.