Myeloid-Derived Suppressor Cells as a Vehicle for Tumor-Specific Oncolytic Viral Therapy

Abstract

One of the several impediments to effective oncolytic virus therapy of cancer remains a lack of tumor-specific targeting. Myeloid derived suppressor cells (MDSCs) are immature myeloid cells induced by tumor factors in tumor-bearing hosts. The biodistribution kinetics of MDSC and other immune cell types in a murine hepatic colon cancer model was investigated through the use of tracking markers and magnetic resonance imaging (MRI). MDSCs were superior to other immune cell types in preferential migration to tumors in comparison to other tissues. Based on this observation, we engineered a strain of vesicular stomatitis virus (VSV), an oncolytic rhabdovirus, that bound MDSCs and used them as a delivery vehicle. Improving VSV binding efficiency to MDSCs extended the long-term survival of mice bearing metastatic colon tumors, compared to systemic administration of wild-type VSV alone. Survival was further extended by multiple injections of the engineered virus without significant toxicity. Notably, direct tumor killing was accentuated by promoting MDSC differentiation towards the classically activated M1-like phenotype. Our results offer a preclinical proof of concept for using MDSCs to facilitate and enhance the tumor-killing activity of tumor-targeted oncolytic therapeutics.

Tumor-specific delivery of biologics by a novel T-cell line HOZOT

“…However, stem cell–based delivery systems lack the cell-in-cell invasion property, and the tumor-homing ability of stem cells would be limited to the stromal areas surrounding tumor cells. Although a variety of immune cells, including cytokine-induced killer cells, dendritic cells, and myeloid-derived suppressor cells, can take up viruses, no mechanism to then transmit the viruses to tumor cells has been elucidated202728. In the present study, we examined the novel HOZOT line of human T cells, which exhibit cell-in-cell invasion and subsequent cytotoxic effects against tumor cells.…”

Recent advances in vesicular stomatitis virus-based oncolytic virotherapy: a 5-year update

“…MDSCs are superior to other immune cell types in preferential migration to tumours in comparison to other tissues. Improving VSV binding efficiency to MDSCs extended the long-term survival of mice bearing metastatic colon tumours compared to systemic administration of WT VSV alone [146].…”

Molecular Pathways: Targeting Tumor-Infiltrating Myeloid-Derived Suppressor Cells for Cancer Therapy

“…As discussed above, an important aspect in the biology of MDSCs is their capability to massively infiltrate almost all types of tumors, and to reach peripheral metastatic sites. Intriguingly, administration of MDSCs loaded with the VSV oncolytic virus (vesicular stomatitis virus) to colon carcinoma-bearing mice significantly prolonged their survival by inducing tumor response as compared with systemic viral therapy (43). Furthermore, injection of MDSCs infected with a radioactive form of Listeria monocytogenes (Listeria at ) led to complete elimination of metastasis and significant reduction of tumor growth in mice bearing pancreatic tumors (44).…”