Therapeutic potential of CAR-T cell-derived exosomes: a cell-free modality for targeted cancer therapy

Abstract

Chimeric antigen receptor (CAR)-based T-cell adoptive immunotherapy is a distinctively promising therapy for cancer. The engineering of CARs into T cells provides T cells with tumor-targeting capabilities and intensifies their cytotoxic activity through stimulated cell expansion and enhanced cytokine production. As a novel and potent therapeutic modality, there exists some uncontrollable processes which are the potential sources of adverse events. As an extension of this impactful modality, CAR-T cell-derived exosomes may substitute CAR-T cells to act as ultimate attackers, thereby overcoming some limitations. Exosomes retain most characteristics of parent cells and play an essential role in intercellular communications via transmitting their cargo to recipient cells. The application of CAR-T cell-derived exosomes will make this cell-based therapy more clinically controllable as it also provides a cell-free platform to diversify anticancer mediators, which responds effectively to the complexity and volatility of cancer. It is believed that the appropriate application of both cellular and exosomal platforms will make this effective treatment more practicable.

Role of stem cell derived exosomes in tumor biology

“…Both CSCs and MSCs are known to secrete nanoscale vesicles or exosomes. Exosomes are 30–100 nm membrane vesicles, released from many cell types in tumors including but not limited to cancer cells, endothelial cells, and immune cells . Exosome cargo mainly contains DNA, proteins, lipids, mRNAs and miRNAs.…”

“…Exosomes are 30-100 nm membrane vesicles, released from many cell types in tumors including but not limited to cancer cells, endothelial cells, and immune cells. [21][22][23] Exosome cargo mainly contains DNA, proteins, lipids, mRNAs and miRNAs. Mechanistically, exosome released from cell-of-origin facilitates intercellular communication either by direct cellular uptake or internalization via a target cell receptor in recipient cell.…”

Exosome-Based Cancer Therapy: Implication for Targeting Cancer Stem Cells

“…They are biocompatible, non-cytotoxic, low immunogenic, simple to produce, easy to store, have a long life span, and high cargo loading capacity (Munagala et al, 2016; Srivastava et al, 2016; Wang et al, 2016b). These characteristics make exosomes a promising drug carrier for cancer treatment (Tian et al, 2013; Tang et al, 2015; Pitt et al, 2016). In this review, we provide an overview for exosome studies with a particular emphasis on current advances of exosome-mediated cancer targeting therapy.…”

Serum exosomes of chronic gastritis patients infected withHelicobacter pylorimediate IL-1α expression via IL-6 trans-signalling in gastric epithelial cells

“…Exosomes are the smallest vesicles (40-150 nm) released from many cell types, including cancer cells, endothelial cells and immune cells, and are generated by the fusion of multi-vesicular bodies containing intraluminal vesicles with the plasma membrane [11][12][13][14]. EVs are subdivided into exosomes, microvesicles and apoptotic bodies.…”

“…EVs are subdivided into exosomes, microvesicles and apoptotic bodies. Exosomes are the smallest vesicles (40-150 nm) released from many cell types, including cancer cells, endothelial cells and immune cells, and are generated by the fusion of multi-vesicular bodies containing intraluminal vesicles with the plasma membrane [11][12][13][14]. Recently, many studies have focused on the role of EVs in the regulation of different pathophysiological conditions, such as cancer [15], immunological disorders [16] and other systematic disorders in different organs.…”