Tumor-targeting Salmonella typhimurium A1-R is a highly effective general therapeutic for undifferentiated soft tissue sarcoma patient-derived orthotopic xenograft nude-mouse models

Author:

Igarashi, Kentaro

Kawaguchi, Kei

Kiyuna, Tasuku

Miyake, Kentaro

Miyake, Masuyo

Singh, Arun S

Eckardt, Mark A

Nelson, Scott D

Russell, Tara A

Dry, Sarah M

Li, Yunfeng

Yamamoto, Norio

Hayashi, Katsuhiro

Kimura, Hiroaki

Miwa, Shinji

Tsuchiya, Hiroyuki

Singh, Shree Ram

Eilber, Fritz C

Hoffman, Robert M
Author Address

AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan., AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA., Division of Hematology-Oncology, University of California, Los Angeles, CA, USA., Department of Surgery, Yale School of Medicine, New Haven, CT, USA., Department of Pathology, University of California, Los Angeles, CA, USA., Division of Surgical Oncology, University of California, Los Angeles, CA, USA., Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA. Electronic address: singhshr@mail.nih.gov., Division of Surgical Oncology, University of California, Los Angeles, CA, USA. Electronic address: fceilber@mednet.ucla.edu., AntiCancer, Inc., San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA. Electronic address: all@anticancer.com.,

Abstract:

Undifferentiated soft tissue sarcoma (USTS) is a recalcitrant and heterogeneous subgroup of soft tissue sarcoma with high risk of metastasis and recurrence. Due to heterogeneity of USTS, there is no reliably effective first-line therapy. We have generated tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R), which previously showed strong efficacy on single patient-derived orthotopic xenograft (PDOX) models of Ewing's sarcoma and follicular dendritic cell sarcoma. In the present study, tumor resected from 4 patients with a biopsy-proven USTS (2 undifferentiated pleomorphic sarcoma [UPS], 1 undifferentiated sarcoma not otherwise specified [NOS] and 1 undifferentiated spindle cell sarcoma [USS]) were grown orthotopically in the biceps femoris muscle of mice to establish PDOX models. One USS model and one UPS model were doxorubicin (DOX) resistant. One UPS and the NOS model were partially sensitive to DOX. DOX is first-line therapy for these diseases. S. typhimurium A1-R arrested tumor growth all 4 models. In addition to arresting tumor growth in each case, S. typhimurium A1-R was significantly more efficacious than DOX in each case, thereby surpassing first-line therapy. These results suggest that S. typhimurium A1-R can be a general therapeutic for USTS and possible sarcoma in general. Copyright © 2018. Published by Elsevier Inc.

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