Combination of NKT cell immunotherapy and oncolytic vesicular stomatitis virus expressing FAST proteins clears metastatic triple negative breast cancer
Adam Nelson 1,2; Brent Johnston 1,2
Triple negative breast cancer is an aggressive type of breast cancer that lacks targeted therapies. It has a poor survival rate due to frequent metastasis to other tissues. Therefore, it is essential to develop therapeutics that can effectively target breast cancer metastases. Using an experimental model of metastatic breast cancer, we examined natural killer T (NKT) cell immunotherapy in combination with recombinant oncolytic vesicular stomatitis virus (VSVΔM51) engineered to express the reovirus FAST proteins p14 (VSV-p14) or p15 (VSV-p15). 4T1 cells were injected into the mammary fat pad of BALB/c mice. Primary tumors were resected on day 12 and followed by intravenous injections with VSV-GFP, VSV-p14 or VSV-p15 on days 13, 15 and 17. NKT cell activation was induced on day 18 via the intravenous administration of dendritic cells loaded with α-galactosylceramide. NKT cell activation in combination with VSV-p14 or VSV-p15 enhanced overall survival compared to individual treatments or NKT cell activation in combination with VSV-GFP. Combination treatment with VSV-p14 or VSV-p15 led to 100% survival and complete metastatic clearance, however VSV-p15 was effective using a 10-fold lower infectious dose. This study demonstrates that NKT cell immunotherapy and VSV-p14 or VSV-p15 can be effectively combined to clear metastatic breast cancer.
Adam Nelson 1,2; Brent Johnston 1,2
- Department of Microbiology & Immunology, Dalhousie University, Halifax, Nova Scotia, Canada
- Beatrice Hunter Cancer Research Institute, Halifax, Nova Scotia, Canada
Triple negative breast cancer is an aggressive type of breast cancer that lacks targeted therapies. It has a poor survival rate due to frequent metastasis to other tissues. Therefore, it is essential to develop therapeutics that can effectively target breast cancer metastases. Using an experimental model of metastatic breast cancer, we examined natural killer T (NKT) cell immunotherapy in combination with recombinant oncolytic vesicular stomatitis virus (VSVΔM51) engineered to express the reovirus FAST proteins p14 (VSV-p14) or p15 (VSV-p15). 4T1 cells were injected into the mammary fat pad of BALB/c mice. Primary tumors were resected on day 12 and followed by intravenous injections with VSV-GFP, VSV-p14 or VSV-p15 on days 13, 15 and 17. NKT cell activation was induced on day 18 via the intravenous administration of dendritic cells loaded with α-galactosylceramide. NKT cell activation in combination with VSV-p14 or VSV-p15 enhanced overall survival compared to individual treatments or NKT cell activation in combination with VSV-GFP. Combination treatment with VSV-p14 or VSV-p15 led to 100% survival and complete metastatic clearance, however VSV-p15 was effective using a 10-fold lower infectious dose. This study demonstrates that NKT cell immunotherapy and VSV-p14 or VSV-p15 can be effectively combined to clear metastatic breast cancer.