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Novel Vaccinia Virus GLV-1h153 is Effective in Treating Metastatic Triple-Negative Breast Cancer In Vivo
Sepideh Gholami*1, Chun-Hao Chen*1, Marina A De Brot*1, Emil Lou*2, Andrew A Marano*1, Kelly M Mojica*1, Jennifer E Nnoli*1, Laura A Daly*1, Laurence J Belin*1, Yuman Fong1
1Memorial Sloan-Kettering Cancer Center, New York, NY;2University of Minnesota, Minneapolis, MN

OBJECTIVE(S):
Triple-negative breast cancers (TNBC) are aggressive, highly metastatic tumors that lack the benefit of targeted therapy. Oncolytic viruses are therapeutic agents which infect, replicate within, and lyse cancer cells. We investigated the therapeutic impact of a novel vaccinia virus, GLV-1h153, in treating metastatic TNBC in an established orthotopic metastatic murine model.
METHODS:
GLV-1h153 was tested against 4 TNBC cell lines. Cytotoxicity and viral replication were determined. Mammary fat pad tumors were generated in athymic nude mice. Xenografts were treated with GLV-1h153 or PBS and analyzed for tumor growth. Tumors and lymph nodes were harvested, fixed and stained with hematoxylin and eosin, and reviewed by a pathologist.
RESULTS:
GFP expression, a measure of viral replication, showed that infection was time- and concentration-dependent. Greater than 90% cell kill was achieved in all cell lines by day 5. GLV-1h153 replicated efficiently in all cell lines with a peak titer of 2.6 x107 viral plaque forming units/ml (>1300-fold increase). In vivo, mean volume of tumors after 2 weeks of treatment was 21 versus 273 mm3 in controls (p=0.002). Frequency of positive lymph nodes was higher in control compared to treated xenografts (67% vs 0%, respectively, p<0.05). No residual tumor was observed in treated mice on histopathology.
CONCLUSIONS:
Our study shows that TNBC are susceptible to infection and cell death by GLV-1h153 in vitro and in vivo. We demonstrated that GLV-1h153 targets lymphatic structures and treats metastatic disease. We believe that GLV-1h153 merits further investigation as a novel therapeutic approach for metastatic TNBC.


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