Related Experiment Video
Updated: May 12, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Myeloid-derived suppressor cells as a vehicle for tumor-specific oncolytic viral therapy
Samuel Eisenstein1, Brian A Coakley, Karen Briley-Saebo
1Department of Oncological Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA.
Abstract:
One of the several impediments to effective oncolytic virus therapy of cancer remains a lack of tumor-specific targeting. Myeloid-derived suppressor cells (MDSC) 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 MRI. MDSCs were superior to other immune cell types in preferential migration to tumors in comparison with other tissues. On the basis of 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 with 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.
Insights
Researchers engineered vesicular stomatitis virus (VSV) to target myeloid-derived suppressor cells (MDSCs), enhancing oncolytic virus therapy for colon cancer. This approach improved tumor targeting and extended survival in preclinical models.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Effective oncolytic virus therapy is limited by poor tumor-specific targeting.
- Myeloid-derived suppressor cells (MDSCs) are immune cells that accumulate in tumors.
Purpose of the Study:
- To investigate the potential of using MDSCs as a delivery vehicle for oncolytic viruses.
- To engineer vesicular stomatitis virus (VSV) for enhanced MDSC binding and tumor targeting.
Main Methods:
- Tracking markers and MRI were used to study immune cell biodistribution in a murine hepatic colon cancer model.
- A VSV strain was engineered to bind MDSCs, utilizing them for viral delivery to tumors.
- The efficacy and toxicity of engineered VSV were evaluated in tumor-bearing mice.
Main Results:
- MDSCs demonstrated preferential migration to tumors compared to other immune cells.
- Engineered VSV showed improved binding to MDSCs, leading to enhanced tumor targeting.
- Improved VSV-MDSC binding significantly extended long-term survival in mice with metastatic colon tumors.
- Multiple injections of engineered VSV demonstrated extended survival without significant toxicity.
- Oncolytic activity was enhanced by promoting MDSC differentiation towards an M1-like phenotype.
Conclusions:
- MDSCs can be effectively utilized as natural carriers for oncolytic viruses.
- Engineered VSV targeting MDSCs offers a promising strategy for improving oncolytic virotherapy efficacy.
- This preclinical study provides a proof-of-concept for MDSC-mediated delivery of oncolytic therapeutics to enhance cancer treatment.
More Related Videos
14:15Preparation of Myeloid Derived Suppressor Cells (MDSC) from Naive and Pancreatic Tumor-bearing Mice using Flow Cytometry and Automated Magnetic Activated Cell Sorting (AutoMACS)
Published on: June 18, 2012
08:52Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant
Published on: May 27, 2011
