TY - JOUR
T1 - Nontoxic radioactive Listeriaat is a highly effective therapy against metastatic pancreatic cancer
AU - Quispe-Tintaya, Wilber
AU - Chandra, Dinesh
AU - Jahangir, Arthee
AU - Harris, Matthew
AU - Casadevall, Arturo
AU - Dadachova, Ekaterina
AU - Gravekamp, Claudia
PY - 2013/5/21
Y1 - 2013/5/21
N2 - 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, 188Rhenium, to an attenuated (at) live Listeria monocytogenes (Listeriaat) 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 Listeriaat 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.
AB - 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, 188Rhenium, to an attenuated (at) live Listeria monocytogenes (Listeriaat) 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 Listeriaat 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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U2 - 10.1073/pnas.1211287110
DO - 10.1073/pnas.1211287110
M3 - Article
C2 - 23610422
AN - SCOPUS:84878123970
SN - 0027-8424
VL - 110
SP - 8668
EP - 8673
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 21
ER -