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- W2564100530 abstract "Oligometastatic (OM) disease represents an intermediate stage of progression between fully systemic metastasized disease and localized tumor burden. Clinical data is emerging that patients with OM are potentially curable, in part because of advances in the precision of radiation therapy treatment, and in part because of advances in the efficacy of immunotherapy on low burden systemic disease. We developed a model of OM melanoma by challenging mice both locally (subcutaneous injection) and systemically (intravenous injection) with B16 melanoma cells, resulting in both local tumor burden and a small number of prominent, systemically distributed lung metastases. We used this model to investigate whether systemic viroimmunotherapy, using Vesicular Stomatitis Virus (VSV) expressing tumor associated antigens to treat low level metastatic tumor burden, could be combined with clinically relevant stereotactic body radiation therapy (SBRT) to treat advanced local disease. In this respect, mice treated with only one treatment modality (systemic VSV-TAA, or local SBRT) needed to be sacrificed reproducibly due to progression of the untreated disease (local tumor or systemic metastatic disease, respectively). In contrast, mice treated with a combination of VSV-TAA and SBRT entered long-term remission resulting in apparent cure of tumor in up to 100% of mice depending upon the experiment. Increased lymphocyte, and CD45+ leukocyte infiltration was observed in tumors following both SBRT and VSV therapy 6-10 days following therapy. Experiments to delineate the role of immune cell subsets in the successful therapy are underway. In a significant proportion of mice, systemic VSV-TAA therapy was able to control local tumor, provided it was small at the start of therapy. SBRT was rarely able to have an impact upon the treatment of metastatic disease suggesting that, in this model, radiotherapy was not the dominant immunotherapy. However, treating mice with VSV-TAA was able to stimulate a detectable anti-tumor T-cell IFN-γ memory response. We plan to further investigate the immunogenicity of VSV-TAA treatment in the context of SBRT as part of a prime-boost immunotherapy strategy for OM disease. Therefore, we have developed a successful therapeutic regime to treat oligometastic disease that combines both radiotherapy to treat local disease, and systemic viroimmunotherapy to treat low-level metastatic disease and further studies to potentiate the anti-tumor effector response in vivo are in progress." @default.
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- W2564100530 date "2015-05-01" @default.
- W2564100530 modified "2023-09-26" @default.
- W2564100530 title "418. Effective Treatment of Oligometastatic Melanoma Using Combination VSV Viroimmunotherapy and Stereotactic Radiotherapy" @default.
- W2564100530 doi "https://doi.org/10.1016/s1525-0016(16)34027-8" @default.
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