Tumor-targeting Salmonella typhimurium A1-R is a highly effective general therapeutic for undifferentiated soft tissue sarcoma patient-derived orthotopic xenograft nude-mouse models.
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 possibly sarcoma in general.
['Igarashi|Kentaro|K|', 'Kawaguchi|Kei|K|', 'Kiyuna|Tasuku|T|', 'Miyake|Kentaro|K|', 'Miyake|Masuyo|M|', 'Singh|Arun S|AS|', 'Eckardt|Mark A|MA|', 'Nelson|Scott D|SD|', 'Russell|Tara A|TA|', 'Dry|Sarah M|SM|', 'Li|Yunfeng|Y|', 'Yamamoto|Norio|N|', 'Hayashi|Katsuhiro|K|', 'Kimura|Hiroaki|H|', 'Miwa|Shinji|S|', 'Tsuchiya|Hiroyuki|H|', 'Singh|Shree Ram|SR|', 'Eilber|Fritz C|FC|', 'Hoffman|Robert M|RM|']
D000368:Aged D000818:Animals D018414:CD8-Positive T-Lymphocytes D004317:Doxorubicin D005260:Female D049452:Green Fluorescent Proteins D064593:Heterografts D006801:Humans D008297:Male D051379:Mice D008819:Mice, Nude D008875:Middle Aged D009369:Neoplasms D012480:Salmonella Infections D012486:Salmonella typhimurium D012509:Sarcoma
Tumor-targeting Salmonella typhimurium A1-R Efficacy PDOX Drug resistant Soft-tissue sarcoma