Vaccinia virus GLV-1h153 is effective in treating and preventing metastatic triple-negative breast cancer

Gholami, Sepideh, Chen, Chun-Hao, Lou, Emil, De Brot, Marina, Fujisawa, Sho, Chen, Nanhai G, Szalay, Aladar A, Fong, Yuman (September 2012) Vaccinia virus GLV-1h153 is effective in treating and preventing metastatic triple-negative breast cancer. In: 132nd ASA Annual Meeting.

DOI: 10.1097/SLA.0b013e3182654572


OBJECTIVE: This study aimed to investigate the therapeutic impact of a new oncolytic vaccinia virus in a triple-negative breast cancer (TNBC) murine model and its potential for treating distant metastatic disease. BACKGROUND: TNBCs are aggressive tumors associated with a high metastatic rate. Their lack of targets for hormonal/biological therapy presents significant clinical challenges and a dire need for novel therapies. METHODS: GLV-1h153, a replication-competent vaccinia virus, was tested against multiple cell lines. Cytotoxicity and viral replication were determined. Intratumoral (IT) or intravenous (IV) injection of GLV-1h153 (1 × 10(7) plaque-forming units) or phosphate buffered saline was tested in an orthotopic murine model, which reliably produces systemic metastasis. Tumors, lymph nodes, and metastatic organs (lung, liver, and brain) were harvested 5 and 8 weeks after treatment and prepared for histopathological review. Demonstration of metastasis was performed using immunofluorescence and hematoxylin and eosin (H&E) staining. RESULTS: GLV-1h153 infected, replicated in, and killed all TNBC cell lines in vitro. In vivo, mean tumor volume 2 weeks after treatment was 22 (IT), 29 (IV) versus 245 mm(3) (control; P < 0.002). Five weeks after treatment, all harvested lymph nodes and organs showed no evidence of metastatic cells. All harvested tumors showed complete response to treatment, with only necrosis and fibrosis on H&E staining 8 weeks after treatment. CONCLUSIONS: This is the first study to demonstrate that TNBCs are killed by a novel vaccinia virus both in vitro and in vivo. Our results suggest that GLV-1h153 is a promising therapeutic agent for preventing and treating metastatic TNBC and warrants further clinical testing in patients.

Item Type: Conference or Workshop Item (Paper)
Subjects: diseases & disorders > cancer > cancer types > breast cancer
CSHL Authors:
Communities: CSHL labs > Gholami Lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: September 2012
Date Deposited: 27 Sep 2023 18:42
Last Modified: 27 Sep 2023 18:42
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