Extracellular Vesicles and Their Current Role in Cancer Immunotherapy

Abstract

Extracellular vesicles (EVs) are natural particles formed by the lipid bilayer and released from almost all cell types to the extracellular environment both under physiological conditions and in presence of a disease. EVs are involved in many biological processes including intercellular communication, acting as natural carriers in the transfer of various biomolecules such as DNA, various RNA types, proteins and different phospholipids. Thanks to their transfer and targeting abilities, they can be employed in drug and gene delivery and have been proposed for the treatment of different diseases, including cancer. Recently, the use of EVs as biological carriers has also been extended to cancer immunotherapy. This new technique of cancer treatment involves the use of EVs to transport molecules capable of triggering an immune response to damage cancer cells. Several studies have analyzed the possibility of using EVs in new cancer vaccines, which represent a particular form of immunotherapy. In the literature there are only few publications that systematically group and collectively discuss these studies. Therefore, the purpose of this review is to illustrate and give a partial reorganization to what has been produced in the literature so far. We provide basic notions on cancer immunotherapy and describe some clinical trials in which therapeutic cancer vaccines are tested. We thus focus attention on the potential of EV-based therapeutic vaccines in the treatment of cancer patients, overviewing the clinically relevant trials, completed or still in progress, which open up new perspectives in the fight against cancer.

Scalable Production of Extracellular Vesicles and Its Therapeutic Values: A Review

“…Currently, researchers are focusing on utilizing exosomes produced by cancer cells as cancer vaccines and utilizing exosomes derived from microorganisms, as well as engineered cells, as vaccines to protect the host against infectious diseases [ 99 , 100 , 101 ]. The EV-based vaccine against cancer has garnered the most attention for preventing tumor development or treating existing tumors [ 102 ]. Compared with conventional vaccines, EV-based vaccines offer unique traits valuable in vaccine design, such as better biosafety and efficiency as antigen-presenting systems and adjuvants [ 103 ].…”

“…Currently, researchers are focusing on utilizing exosomes produced by cancer cells as cancer vaccines and utilizing exosomes derived from microorganisms, as well as engineered cells, as vaccines to protect the host against infectious diseases [99][100][101]. The EV-based vaccine against cancer has garnered the most attention for preventing tumor development or treating existing tumors [102].…”

Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems

“…Other common associated markers include LOX [173][174][175], MMP [173][174][175], Twist [176,177], STAT3/IL-6 [178][179][180][181][182][183], MAPK/ERK [184][185][186], Sox-2 [187][188][189][190], Oct-4 [191][192][193], and c-Myc [194][195][196][197]. While the HIF family remains the primary mediators of the hypoxic response, research also points towards exosomal involvement in various hypoxic functionalities [151,[198][199][200][201]. Given their vesicular nature, exosomes' involvement in the TME does shine light on the possibility of their usage as next-gen NCs, specifically in the context of CSC-targeting.…”

Bladder Cancer Extracellular Vesicles Elicit a CD8 T Cell-Mediated Antitumor Immunity

“…The application of both natural and bioengineered EVs, as well as artificial EV-like nanoparticles for therapeutic delivery systems, has been a topic of growing interest due to their nano-scale size, natural origin and ability to encapsulate various biomolecules within the lipid bilayer membrane. EVs, including certain TEVs, have been proposed to serve as a cancer vaccine given that they naturally carry antigenic peptides capable of eliciting antitumor immune responses [ 19 , 20 ], yet this idea has not been tested in BC. In this current study, we applied a preclinical MB49 syngeneic mouse model and found that BC-derived EVs are immunoactive and can prevent autologous tumor growth through a mechanism primarily mediated by CD8 + T lymphocytes.…”