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.
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.
Authors: Sepideh Gholami; Andrew Marano; Nanhai G Chen; Richard J Aguilar; Alexa Frentzen; Chun-Hao Chen; Emil Lou; Sho Fujisawa; Clarisse Eveno; Laurence Belin; Pat Zanzonico; Aladar Szalay; Yuman Fong Journal: Breast Cancer Res Treat Date: 2014-11-13 Impact factor: 4.872
Authors: S Gholami; C-H Chen; S Gao; E Lou; S Fujisawa; J Carson; J E Nnoli; T-C Chou; J Bromberg; Y Fong Journal: Cancer Gene Ther Date: 2014-06-13 Impact factor: 5.987
Authors: Clarisse Eveno; Kelly Mojica; Justin W Ady; Daniel L J Thorek; Valerie Longo; Laurence J Belin; Sepideh Gholami; Clark Johnsen; Pat Zanzonico; Nanhai Chen; Tony Yu; Aladar A Szalay; Yuman Fong Journal: Surgery Date: 2015-02 Impact factor: 3.982
Authors: Laurence J Belin; Justin W Ady; Christina Lewis; Drew Marano; Sepideh Gholami; Kelly Mojica; Clarisse Eveno; Valerie Longo; Pat B Zanzonico; Nanhai G Chen; Aladar A Szalay; Yuman Fong Journal: Surgery Date: 2013-07-23 Impact factor: 3.982
Authors: Daniel L Price; Pingdong Li; Chun-Hao Chen; Danni Wong; Zhenkun Yu; Nanhai G Chen; Yong A Yu; Aladar A Szalay; Joseph Cappello; Yuman Fong; Richard J Wong Journal: Head Neck Date: 2015-06-16 Impact factor: 3.147