Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1783606857634414592 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7646835 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT kazmierczakroberta evaluationsofcrc2631toxicitytumorcolonizationandgeneticstabilityinthetrampprostatecancermodel AT dhagatmehtabakul evaluationsofcrc2631toxicitytumorcolonizationandgeneticstabilityinthetrampprostatecancermodel AT guldenelke evaluationsofcrc2631toxicitytumorcolonizationandgeneticstabilityinthetrampprostatecancermodel AT leeli evaluationsofcrc2631toxicitytumorcolonizationandgeneticstabilityinthetrampprostatecancermodel AT malixin evaluationsofcrc2631toxicitytumorcolonizationandgeneticstabilityinthetrampprostatecancermodel AT davisstoberclintinp evaluationsofcrc2631toxicitytumorcolonizationandgeneticstabilityinthetrampprostatecancermodel AT barnettaustena evaluationsofcrc2631toxicitytumorcolonizationandgeneticstabilityinthetrampprostatecancermodel AT chabuyvesc evaluationsofcrc2631toxicitytumorcolonizationandgeneticstabilityinthetrampprostatecancermodel |