Extracellular Vesicles for Cancer Therapy: Impact of Host Immune Response

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.

Exosomes of mesenchymal stem cells as nano-cargos for anti-SARS-CoV-2 asRNAs

“…They can interact with macromolecules and serve as distributors for proteins, lipids, mRNA, miRNA, and DNA (48). Exosomes may interact with the host's immune system, so the selection of the parent cell for exosome production needs to be performed carefully (49). Application of human exosomes for treatment of diseases was tested in clinical trials (50) and has a developing market (51).…”

Molecular Insights into the Potential of Extracellular Vesicles Released from Mesenchymal Stem Cells and Other Cells in the Therapy of Hematologic Malignancies

“…The small size of EVs enables them to cross the blood-brain barrier; the high similarity between the EV membrane and cellular membrane makes the former immune-tolerable, and the architecture of EVs protects their cargo from the degradation action by nucleases and proteases [ 95 , 96 ]. These three features have made EVs an attractive mean for drug delivery.…”

Nanoparticle-Based Delivery of Tumor Suppressor microRNA for Cancer Therapy

“…However, since MSCs are principally regenerative cells and secrete abundant growth factors and chemokines, there are concerns that MSCs may be pro-tumorigenic in some scenarios [43]. Since EVs are believed to represent a fingerprint of the secreting cell, EVs released by MSCs (MSC-EVs) could potentially have the same tumor-targeting and immune evasion capabilities [44,45]. Given the natural packaging of miRNAs into EVs, researchers have engineered MSC-EVs to enrich for tumor-suppressing miRNAs, miR-146b, miR-185 or miR-379, followed by either local (topical or intratumoral (IT)) [30,36] or systemic (IV) [12] administration.…”