Emerging Prospects of Exosomes for Cancer Treatment: From Conventional Therapy to Immunotherapy

Abstract

remains unclear how and why cancer occurs and progresses. Using an evolutionary approach, the concept of a complex adaptive system (CAS) was developed to describe the behaviors of cancer tumorigenesis, [2] which may suggest a frameshift away from the limitations of current approaches that mainly address the importance of alteration in specific target molecules in cancer cells. This change in perspectives toward tumors, not simply as a disease to be cured but also as CAS, is expected to be the cornerstone of the paradigm shift toward innovative cancer therapies. [3] The human immune system can also be viewed as a CAS and therefore expected to initiate self-defense mechanisms against cancer in a complex adaptive manner as long as it recognizes the cancer cells as the non-self-signals. Consequently, the key to controlling cancer could lie in understanding how to manipulate the immune system and strengthen its defenses against cancer. The concept of facilitating the immune system to fight against cancer was first suggested in the late 1800s by Dr. Wiliam Coley, who was the first to observe anti-tumor effects after intratumoral injection of microbe-derived toxins. [4] Since then, the field of cancer immunotherapy research has flourished, resulting in clinical achievements such as immune checkpoint blockades and chimeric antigen receptor T cell (CAR-T) therapy. [5] However, immune suppression resistance mechanisms have simultaneously been identified that have impeded favorable response to cancer immunotherapy. [6,7] Exosome-based cancer therapies have emerged as a potential option for overcoming these limitations to the effects of current cancer therapies due to their pathophysiological efficacy against tumors. [8] Exosomes are secreted externally by cells and are found ubiquitously in blood, urine, saliva, cerebrospinal fluid, pleural fluid, and breast milk. [9,10] The distinction between different types of extracellular vesicles (EVs) is unclear; however, they are conventionally classified as either ectosomes (microvesicles or microparticles) or exosomes. [11] While ectosomes are formed by the outward budding of the plasma membrane, exosomes are formed from multivesicular bodies (MVB) containing intraluminal vesicles via inward budding of the late endosome, which later fuses to the membrane. The formed vesicles are then secreted via a process known as exocytosis (Figure 1). The two types of vesicle also differ in diameter, Exosomes are a class of extracellular vesicles of around 100 nm in diameter that are secreted by most cells and contain various bioactive molecules reflecting their cellular origin and mediate intercellular communication. Studies of these exosomal features in tumor pathogenesis have led to the development of therapeutic and diagnostic approaches using exosomes for cancer therapy. Exosomes have many advantages for conveying therapeutic agents such as small interfering RNAs, microRNAs, membrane-associated proteins, and chemotherapeutic compounds; thus, they are considered a prime candidate as a deliv...

Role of exosomes in the immune microenvironment of ovarian cancer (Review)

“…Small interfering RNAs and miRNAs carried by exosomes target and inhibit tumor cell proliferation and drug resistance (175). The reorganization of the exosomal membrane can improve the efficiency of drug loading and the sustained release of drugs (189). Exosomes can overcome the weak immunogenicity of tumor antigens that are likely to be used in a cancer vaccine (190).…”

Emerging Role of Exosomes in Retinal Diseases

“…Owing to the relatively small volume vitreous and aqueous humor can be obtained, and for ethic issues, most research is still at the stage, mainly performed in vitro . On the other hand, retina, as the immune-privileged site, which is protected from external and internal insults by its blood-retina barriers and immune suppressive microenvironment, is actually an ideal target tissue for exosome-based therapies ( Nam et al, 2020 ).…”

Biological membrane derived nanomedicines for cancer therapy

“…The precursors of exosomes are generated by plasma membrane by several steps of maturations and finally released to the extracellular space [102]. As a type of natural carriers of different cargos in the communication between cells, exosomes possess the features of high biocompatibility, immune evasion ability, and innate interactions with tumor cells [32,103]. Attributing to the advantages of exosomes as natural secreted, nanosized bio-carriers, additional modifications on exosomes to develop novel nanomedicines are promising [100].…”

“…Exosomes carry similar membrane proteins to their donor cells, thus the bioengineering of exosomes can be realized by transfecting or modifying the donor cells [32,103]. Based on this, Wang et al [104] developed a specific tumor targeting chemo-photothermal therapy via bioengineered exosomes (Figure 7).…”

“…Another attractive direction is to prepare anti-tumor nanomedicines by directly utilizing engineered cell membrane-derived vesicles or nanovesicles secreted by cells [3,[27][28][29][30][31]. Exosomes are nanovesicles secreted by eukaryotic cells with high stability and good biocompatibility [32]. More intriguingly, exosomes derived from tumor cells can intrinsically target homological cells owing to the proteins on their membrane surfaces [30], which make them capable to be bioengineered into drug delivery platforms with excellent targeting ability.…”