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Evaluations of CRC2631 toxicity, tumor colonization, and genetic stability in the TRAMP prostate cancer model

Conventional cancer chemotherapies are not fully efficacious and do not target tumors, leading to significant treatment-related morbidities. A number of genetically attenuated cancer-targeting bacteria are being developed to safely target tumors in vivo. Here we report the toxicological, tumor-targe...

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Autores principales: Kazmierczak, Robert A., Dhagat-Mehta, Bakul, Gulden, Elke, Lee, Li, Ma, Lixin, Davis-Stober, Clintin P., Barnett, Austen A., Chabu, Yves C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646835/
https://www.ncbi.nlm.nih.gov/pubmed/33216833
http://dx.doi.org/10.18632/oncotarget.27769
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author Kazmierczak, Robert A.
Dhagat-Mehta, Bakul
Gulden, Elke
Lee, Li
Ma, Lixin
Davis-Stober, Clintin P.
Barnett, Austen A.
Chabu, Yves C.
author_facet Kazmierczak, Robert A.
Dhagat-Mehta, Bakul
Gulden, Elke
Lee, Li
Ma, Lixin
Davis-Stober, Clintin P.
Barnett, Austen A.
Chabu, Yves C.
author_sort Kazmierczak, Robert A.
collection PubMed
description Conventional cancer chemotherapies are not fully efficacious and do not target tumors, leading to significant treatment-related morbidities. A number of genetically attenuated cancer-targeting bacteria are being developed to safely target tumors in vivo. Here we report the toxicological, tumor-targeting, and efficacy profiles of Salmonella enterica serovar Typhimurium CRC2631 in a syngeneic and autochthonous TRAMP model of aggressive prostate cancer. CRC2631 preferentially colonize primary and metastatic tumors in the TRAMP animals. In addition, longitudinal whole genome sequencing studies of CRC2631 recovered from prostate tumor tissues demonstrate that CRC2631 is genetically stable. Moreover, tumor-targeted CRC2631 generates an anti-tumor immune response. Combination of CRC2631 with checkpoint blockade reduces metastasis burden. Collectively, these findings demonstrate a potential for CRC2631 in cancer immunotherapy strategies.
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spelling pubmed-76468352020-11-17 Evaluations of CRC2631 toxicity, tumor colonization, and genetic stability in the TRAMP prostate cancer model Kazmierczak, Robert A. Dhagat-Mehta, Bakul Gulden, Elke Lee, Li Ma, Lixin Davis-Stober, Clintin P. Barnett, Austen A. Chabu, Yves C. Oncotarget Research Paper Conventional cancer chemotherapies are not fully efficacious and do not target tumors, leading to significant treatment-related morbidities. A number of genetically attenuated cancer-targeting bacteria are being developed to safely target tumors in vivo. Here we report the toxicological, tumor-targeting, and efficacy profiles of Salmonella enterica serovar Typhimurium CRC2631 in a syngeneic and autochthonous TRAMP model of aggressive prostate cancer. CRC2631 preferentially colonize primary and metastatic tumors in the TRAMP animals. In addition, longitudinal whole genome sequencing studies of CRC2631 recovered from prostate tumor tissues demonstrate that CRC2631 is genetically stable. Moreover, tumor-targeted CRC2631 generates an anti-tumor immune response. Combination of CRC2631 with checkpoint blockade reduces metastasis burden. Collectively, these findings demonstrate a potential for CRC2631 in cancer immunotherapy strategies. Impact Journals LLC 2020-11-03 /pmc/articles/PMC7646835/ /pubmed/33216833 http://dx.doi.org/10.18632/oncotarget.27769 Text en Copyright: © 2020 Kazmierczak et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Kazmierczak, Robert A.
Dhagat-Mehta, Bakul
Gulden, Elke
Lee, Li
Ma, Lixin
Davis-Stober, Clintin P.
Barnett, Austen A.
Chabu, Yves C.
Evaluations of CRC2631 toxicity, tumor colonization, and genetic stability in the TRAMP prostate cancer model
title Evaluations of CRC2631 toxicity, tumor colonization, and genetic stability in the TRAMP prostate cancer model
title_full Evaluations of CRC2631 toxicity, tumor colonization, and genetic stability in the TRAMP prostate cancer model
title_fullStr Evaluations of CRC2631 toxicity, tumor colonization, and genetic stability in the TRAMP prostate cancer model
title_full_unstemmed Evaluations of CRC2631 toxicity, tumor colonization, and genetic stability in the TRAMP prostate cancer model
title_short Evaluations of CRC2631 toxicity, tumor colonization, and genetic stability in the TRAMP prostate cancer model
title_sort evaluations of crc2631 toxicity, tumor colonization, and genetic stability in the tramp prostate cancer model
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646835/
https://www.ncbi.nlm.nih.gov/pubmed/33216833
http://dx.doi.org/10.18632/oncotarget.27769
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