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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Nontoxic radioactive Listeria~(at) is a highly effective therapy against metastatic pancreatic cancer
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Nontoxic radioactive Listeria~(at) is a highly effective therapy against metastatic pancreatic cancer

机译：Nontoxic radioactive Listeria~(at) is a highly effective therapy against metastatic pancreatic cancer

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摘要

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.

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