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Proc Natl Acad Sci U S A. 2013 May 21;110(21):8668-73. doi: 10.1073/pnas.1211287110. Epub 2013 Apr 22.

Nontoxic radioactive Listeria(at) is a highly effective therapy against metastatic pancreatic cancer.

Author information

1
Department of Microbiology and Immunology and Department of Radiology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

Abstract

No significant improvement in therapy of pancreatic cancer has been reported over the last 25 y, underscoring the urgent need for new alternative therapies. Here, we coupled a radioisotope, (188)Rhenium, to an attenuated (at) live Listeria monocytogenes (Listeria(at)) using Listeria-binding antibodies, thus creating a unique radioactive Listeria(at) (RL). We then demonstrated in a highly metastatic pancreatic mouse tumor model (Panc-02) that RL delivered radioactivity to the metastases and less abundantly to primary tumors in vivo, without harming normal cells. This result was possible because Listeria(at) was efficiently cleared by the immune system in normal tissues but not in the heavily immune-suppressed microenvironment of metastases and primary tumor. Multiple treatments with low doses of the RL resulted in a dramatic decrease in the number of metastases (~90%) compared with control groups in the Panc-02 model. This is the first report of using live attenuated bacteria delivering a highly radioactive payload to the metastases, resulting in killing tumor cells in vivo without harming normal cells. The nontoxic RL treatment is attractive for clinical development as a therapy to prevent pancreatic cancer recurrence and metastases.

PMID:
23610422
PMCID:
PMC3666740
DOI:
10.1073/pnas.1211287110
[Indexed for MEDLINE]
Free PMC Article

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