Oncotarget

Research Papers:

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

Robert A. Kazmierczak, Bakul Dhagat-Mehta, Elke Gulden, Li Lee, Lixin Ma, Clintin P. Davis-Stober, Austen A. Barnett and Yves C. Chabu _

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Abstract

Robert A. Kazmierczak1,*, Bakul Dhagat-Mehta1,*, Elke Gulden2, Li Lee3,4, Lixin Ma3,4, Clintin P. Davis-Stober5, Austen A. Barnett6 and Yves C. Chabu7

1 Cancer Research Center, Columbia, MO, USA

2 Department of Immunobiology, Yale University, New Haven, CT, USA

3 Department of Radiology and Department of Physics and Astronomy, University of Missouri, Columbia, MO, USA

4 Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA

5 Department of Psychological Sciences, Institute for Data Science & Informatics, University of Missouri, Columbia, MO, USA

6 Department of Biology, DeSales University, Center Valley, PA, USA

7 Division of Biological Sciences, University of Missouri, Columbia, MO, USA

* These authors contributed equally to this work

Correspondence to:

Yves C. Chabu,email: chabuc@missouri.edu

Keywords: salmonella; cancer targeting; prostate cancer; immunotherapy; TRAMP

Received: July 02, 2020     Accepted: September 24, 2020     Published: November 03, 2020

Copyright: © 2020 Kazmierczak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

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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