title: Nontoxic radioactive Listeria(at) is a highly effective therapy against metastatic pancreatic cancer.
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.
authors.affiliation: Department of Microbiology and Immunology and Department of Radiology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Wilber
authors.initials: W
authors.lastname: Quispe-Tintaya
authors.forename: Dinesh
authors.initials: D
authors.lastname: Chandra
authors.forename: Arthee
authors.initials: A
authors.lastname: Jahangir
authors.forename: Matthew
authors.initials: M
authors.lastname: Harris
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Dadachova
authors.forename: Claudia
authors.initials: C
authors.lastname: Gravekamp
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D007553:Isotope Labeling; D008087:Listeria; D051379:Mice; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000473:pathology / Q000532:radiotherapy*; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011868:Radioisotopes; D012211:Rhenium
chemical_list: D011868:Radioisotopes; D012211:Rhenium