Exosomes as a drug delivery tool for cancer therapy: a new era for existing drugs and oncolytic viruses

ABSTRACTIntroduction Exosomes are cell-derived nanovesicles involved in cell-to-cell communications. These nanovesicles are generally considered to contain important carriers of information such as DNA and RNA, and show specific tropism.Areas covered The combination of existing therapeutic agents with exosomes enhances therapeutic effects by increasing uptake into the tumor. Induction of immunogenic cell death (ICD) may also be triggered more strongly than with the drug alone. Oncolytic viruses (OVs) are even more effective as a drug in combination with exosomes. Although OVs are more likely to cause immune activity, combination with exosomes can exert synergistic effects. OVs have potent anti-tumor effects, but many limitations, such as being limited to local administration and vulnerability to attack by antibodies. Incorporation into exosomes can overcome these limitations and may allow effects against distant tumors.Expert opinion Novel therapies using exosomes are very attractive in terms of enhancing therapeutic efficacy and reducing side effects. This approach also contains elements overcoming disadvantages in OVs, which have not been used clinically until now, and may usher in a new era of cancer treatments.KEYWORDS: Cancer therapychemotherapydrug delivery systemexosomeextracellular vesicleoncolytic virus Article highlights Exosomes are nano-sized particles secreted by various cells.Potent anti-tumor effects can be exerted by increased tumor cell uptake of exosomes loaded with existing agents such as DTX, CDDP, and DOX. This also synergistically enhances ICD.Oncolytic virus-containing exosomes can specifically accumulate in tumors or exert potent anti-tumor effects as a result of increased tumor uptake. They also exert anti-tumor effects specifically on distant tumors through intercellular communications.Exosomes offer promise as a very useful drug delivery tool.Abbreviations CDDP=cisplatinCME=clathrin-mediated endocytosisDTX=docetaxelDOX=doxorubicinEPR=enhanced permeability and retentionEVs=extracellular vesiclesExo-301=exosome-derived tumor cells treated with OBP-301Exo-DTX=DTX-loaded exosomesExo-PTX=PTX-loaded exosomesFDA=The United States Food and Drug AdministrationGC=Gastric cancerHSP=heat shock proteinsHSV-1=herpes simplex type-1 virushTERT=human telomerase reverse transcriptaseICD=immunogenic cell deathISEV=International Society for Extracellular VesiclesL-OHP=oxaliplatinMVBs=multivesicular bodiesnPTX=nab-paclitaxelOAdV=oncolytic adenovirusesOBP-301=telomelysinOVs=oncolytic virusesPDACs=pancreatic ductal adenocarcinomasPTX=paclitaxelTAMs=tumor-associated macrophagesT-VEC=talimogene laherparepvecDeclaration of interestsThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.AcknowledgmentsAll figures were created with BioRender.com.Additional informationFundingThis study was partially supported by SPS KAKENHI Grant [to T. Fujiwara; No. 22H03148, and to Y. Kakiuchi; No. 22K16512].