Tumor-targeting Salmonella typhimurium A1-R overcomes nab-paclitaxel resistance in a cervical cancer PDOX mouse model.

Authors:
Kentaro Miyake
Kentaro Miyake
University of California
Oakland | United States
Takuya Murata
Takuya Murata
University of Tokyo
Japan
Takashi Murakami
Takashi Murakami
AntiCancer
San Diego | United States
Ming Zhao
Ming Zhao
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization
China
Tasuku Kiyuna
Tasuku Kiyuna
AntiCancer
Laghouat | Algeria
Kei Kawaguchi
Kei Kawaguchi
Hachinohe Shimin Hospital
Japan
Kentaro Igarashi
Kentaro Igarashi
Graduate School of Medical Science
Lucknow | India
Masuyo Miyake
Masuyo Miyake
AntiCancer
San Diego | United States

Arch Gynecol Obstet 2019 Jun 5;299(6):1683-1690. Epub 2019 Apr 5.

AntiCancer Inc., San Diego, CA, USA.

Purpose: Cervical cancer is a recalcitrant disease. To help overcome this problem, we previously established a patient-derived orthotopic xenograft (PDOX) model of cervical cancer. In the previous study, we found the tumor to be resistant to nab-paclitaxal (nab-PTX). We also previously developed the tumor-targeting bacteria Salmonella typhimurium A1-R (S. typhimurium A1-R). The aim of the present study was to investigate the efficacy of S. typhimurium A1-R to overcome nab-PTX resistance in the cervical cancer PDOX model.

Methods: Cervical-cancer tumor fragments were implanted orthotopically into the neck of the uterus of nude mice. The cervical-cancer PDOX models were randomized into the following four groups after the tumor volume reached 60 mm: G1: untreated group; G2: nab-PTX (i.v., 10 mg/kg, biweekly, 3 weeks); G3: Salmonella typhimurium A1-R (i.v., 5 × 10 CFU/body, weekly, 3 weeks); G4: nab-PTX combined with Salmonella typhimurium A1-R (nab-PTX, 10 mg/kg, i.v., biweekly, 3 weeks; S. typhimurium A1-R, 5 × 10 CFU/body, i.v., weekly, 3 weeks). Each group comprised eight mice. All mice were sacrificed on day 22. Tumor volume was measured on day 0 and day 22. Body weight was measured twice a week.

Results: Nab-PTX and Salmonella typhimurium A1-R did not show significant efficacy as monotherapy compared to the control group (P = 0.564 and P = 0.120, respectively). In contrast, nab-PTX combined with Salmonella typhimurium A1-R significantly suppressed tumor growth compared to the untreated control group and nab-PTX group (P < 0.001 and P = 0.026, respectively).

Conclusions: Salmonella typhimurium A1-R has potential future clinical application to overcome drug resistance in cervical cancer.

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http://dx.doi.org/10.1007/s00404-019-05147-3DOI Listing
June 2019
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