Nontoxic radioactive Listeriaat is a highly effective therapy against metastatic pancreatic cancer

Wilber Quispe-Tintaya, Dinesh Chandra, Arthee Jahangir, Matthew Harris, Arturo Casadevall, Ekaterina Dadachova, Claudia Gravekamp

Research output: Contribution to journalArticle

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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, 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.

Original languageEnglish (US)
Pages (from-to)8668-8673
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number21
DOIs
StatePublished - May 21 2013

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Listeria
Pancreatic Neoplasms
Neoplasm Metastasis
Neoplasms
Therapeutics
Listeria monocytogenes
Complementary Therapies
Radioisotopes
Radioactivity
Immune System
Bacteria
Recurrence
Control Groups
Antibodies

ASJC Scopus subject areas

  • General

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Nontoxic radioactive Listeriaat is a highly effective therapy against metastatic pancreatic cancer. / Quispe-Tintaya, Wilber; Chandra, Dinesh; Jahangir, Arthee; Harris, Matthew; Casadevall, Arturo; Dadachova, Ekaterina; Gravekamp, Claudia.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 21, 21.05.2013, p. 8668-8673.

Research output: Contribution to journalArticle

Quispe-Tintaya, Wilber ; Chandra, Dinesh ; Jahangir, Arthee ; Harris, Matthew ; Casadevall, Arturo ; Dadachova, Ekaterina ; Gravekamp, Claudia. / Nontoxic radioactive Listeriaat is a highly effective therapy against metastatic pancreatic cancer. In: Proceedings of the National Academy of Sciences of the United States of America. 2013 ; Vol. 110, No. 21. pp. 8668-8673.
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