@article{288eb2702abe470da0db9ae1584f39b4,
title = "Generation of a Tumor-Specific Chemokine Gradient Using Oncolytic Vesicular Stomatitis Virus Encoding CXCL9",
abstract = "Genetically modified vesicular stomatitis virus (VSV) is an attractive agent for cancer treatment due to rapid intratumoral replication and observed clinical responses. Although VSV selectively kills malignant cells and can boost antitumor immunity, limited induction of intratumoral immune infiltration remains a barrier to efficacy in some cancer models. Here we engineered the oncolytic VSV platform to encode the T cell chemokine CXCL9, which is known to mediate the recruitment of activated CD8+ cytotoxic T cells and CD4+ T helper cells, and demonstrates conserved protein function between mice and humans. Chemotactic activity of the virally encoded chemokine was confirmed in vitro. Intratumoral concentration of CXCL9 was shown to increase after VSV therapy in three different cancer models, but to a much greater degree after VSV-CXCL9 therapy as compared with VSV control viruses. Despite a steep chemokine gradient from the tumor to the bloodstream, tumor trafficking of adoptively transferred and endogenous T cells was not measurably increased following VSV-CXCL9 therapy. Our results indicate that oncolytic VSV infection promotes release of CXCL9 in the tumor microenvironment, but further boosting of the functional chemokine gradient through virus engineering has little incremental impact on intratumoral immune cell infiltration in mouse and human tumor models.",
keywords = "CXCL9, chemokine, chemokine gradient, oncolytic virotherapy, vesicular stomatitis virus",
author = "Eckert, {Elizabeth C.} and Nace, {Rebecca A.} and Tonne, {Jason M.} and Laura Evgin and Vile, {Richard G.} and Russell, {Stephen J.}",
note = "Funding Information: LM2 cells were a kind gift from Manish Patel at the University of Minnesota. Activated non-transduced primary T cells were graciously provided by Leo Sakemura from the Laboratory of Saad Kenderian at the Mayo Clinic Rochester. The Mayo Microscopy and Cell Analysis Core was utilized for some of the experiments performed in this report, specifically the flow cytometry experiments. This publication was supported by Grant Number UL1 TR002377 from the National Center for Advancing Translational Sciences (NCATS) and CTSA Grant Number TL1 TR002380 from NCATS . Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Funding Information: LM2 cells were a kind gift from Manish Patel at the University of Minnesota. Activated non-transduced primary T cells were graciously provided by Leo Sakemura from the Laboratory of Saad Kenderian at the Mayo Clinic Rochester. The Mayo Microscopy and Cell Analysis Core was utilized for some of the experiments performed in this report, specifically the flow cytometry experiments. This publication was supported by Grant Number UL1 TR002377 from the National Center for Advancing Translational Sciences (NCATS) and CTSA Grant Number TL1 TR002380 from NCATS. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2020",
month = mar,
day = "27",
doi = "10.1016/j.omto.2019.12.003",
language = "English (US)",
volume = "16",
pages = "63--74",
journal = "Molecular Therapy - Oncolytics",
issn = "2372-7705",
publisher = "Nature Publishing Group",
}