Extracellular Vesicles for Cancer Therapy: Impact of Host Immune Response.

Katie E Gilligan,Róisín M Dwyer

doi:10.3390/cells9010224

Katie E Gilligan, Róisín M Dwyer

Open Access

https://doi.org/10.3390/cells9010224

Copy DOI

Journal: Cells	Publication Date: Jan 16, 2020
Citations: 10	License type: CC BY 4.0

Affiliation: Ollscoil na Gaillimhe – University of Galway

Abstract

In recent times, extracellular vesicles (EVs) have come under the spotlight as potential therapeutics for cancer, due to the relative ease of manipulation of contents and potential for tumor targeting. The use of EVs as delivery vehicles may bypass some of the negative effects associated with cell-based carriers, and there has been a major focus on defining EV subtypes, establishing transparent nomenclature, and isolation and characterization techniques. EVs are believed to be a fingerprint of the secreting cell and so researchers harness the positive aspects of a particular cell of origin, and can then further modify EV contents to improve therapeutic efficacy. In this review, we highlight studies employing EVs as cancer therapeutics that have reported on immune response. As we rapidly advance towards potential application in the clinical setting, the question of immune response to EV administration in the cancer setting has become critically important.

Highlights

While there have been major advances in the field, the potential for activation of a toxic host immune response remains one of the major barriers to cell and gene therapy for cancer [1,2]
Dendritic cell (DC)-derived extracellular vesicles (EVs) and their ability to trigger the immune response as a form of cancer therapy has been widely investigated
EVs secreted by murine DCs expressing α-fetoprotein (DEVAFP ), elicited a strong immune response when injected intravenously, which resulted in decreased tumor growth and increased survival rates for mice

Summary

Introduction

While there have been major advances in the field, the potential for activation of a toxic host immune response remains one of the major barriers to cell and gene therapy for cancer [1,2]. The effect of EVs isolated from the OTSCC cell lines on the cytotoxicity of CD8+ T and Natural Killer (NK) cells from healthy patients was investigated. It was found that the EVs increased cytotoxic activity of the cells, the results varied depending on patient donor, EV parent cell and cancer cell type. In a zebrafish non tumor bearing model, EVs derived from these cell lines were administered, with decreased levels of anti-inflammatory Interleukin (IL)-13 reported. This was interesting as it was previously reported that IL-13 was increased in the saliva of OTSCC patients, suggesting that EVs derived from these cells do not cause this increase in IL-13 [14]. The study concluded that EVs and MSCs may differ in their immune-modulating mechanisms and activities [17]

Employing EVs to Promote an Anti-Tumor Immune Response

Exploiting

Employing EVs to Increase Persistence and Targeting of Therapeutics

Discussion