Registered clinical trials investigating treatment with cell-derived extracellular vesicles: a scoping review

Duong, An Hoai; Parmar, Gaganvir; Kirkham, Aidan M.; Burger, Dylan; Allan, David S.

doi:10.1016/j.jcyt.2023.04.007

Cited by 27 publications

(12 citation statements)

References 29 publications

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“…EVs are nano-sized membrane-bound vesicles that contain cargo from the cell which they originate. Upon interaction with target cells, EVs can mediate therapeutic effects through various mechanisms ( 35 ). Since EVs occur naturally in the bloodstream and tissues, administration of EVs is thought to be safe and elicit few toxic or inflammatory effects, making them a promising new cell-free therapeutic ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles derived from immortalized human natural killer cell line NK3.3 as a novel therapeutic for multiple myeloma

Matchett,

Kornbluth

2023

Front. Immunol.

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IntroductionOver the last decade, there have been many advancements in the therapeutic treatment of multiple myeloma (MM), including the use of natural killer (NK) cells. However, despite promising results from clinical trials, there are concerns over the use of NK cell-based therapy. Cells often undergo growth arrest, limiting their experimental utility; donor cells are extremely heterogeneous, resulting in content variability; and patients receiving allogeneic cells are at risk for graft-versus-host disease and/or cytokine release syndrome. Extracellular vesicles (EVs) have emerged as a new natural therapeutic tool. EVs are known to carry cargo derived from the parent cell from which they originate. NK cells play an important role in the innate immune system, targeting and killing tumor cells. This has led many researchers to isolate EVs from NK cells for their cytotoxic potential.MethodsIn this study, we isolated EVs from the NK cell line, NK3.3, which was derived from the peripheral blood of a healthy donor. Currently, it is the only normal human NK cell line reported with all the functional characteristics of healthy NK cells. To address the issue of growth arrest, we immortalized NK3.3 cells with lentivirus encoding the catalytic subunit of human telomerase htert (NK3.3-LTV). EVs from these cells were isolated using a modified polyethylene glycol (PEG)-acetate precipitation protocol to simplify processing and increase EV yield.Results and conclusionsWe demonstrated that NK3.3-LTV EVs target both sensitive and drug-resistant MM cell lines as well as primary patient MM cells in vitro, decreasing proliferation and inducing apoptotic cell death as well as or better than EVs from non-immortalized cells with no toxicity towards normal cells. This study is the first step towards developing an immunotherapeutic product designed to treat patients with relapsed/refractory MM.

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Section: Discussionmentioning

confidence: 99%

Extracellular vesicles derived from immortalized human natural killer cell line NK3.3 as a novel therapeutic for multiple myeloma

Matchett,

Kornbluth

2023

Front. Immunol.

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“…EVs are involved in diverse biological processes, such as cell motility [ 254 , 255 , 256 ], differentiation [ 257 , 258 , 259 ], proliferation [ 260 , 261 ], apoptosis [ 262 , 263 ], reprogramming [ 264 , 265 , 266 ], and immunity [ 267 , 268 ], through regulation of intercellular communication. Understanding the regulatory mechanisms of EVs in these biological processes and in intercellular communication is crucial for their clinical potential [ 269 , 270 ] and applications [ 271 , 272 , 273 , 274 , 275 , 276 , 277 , 278 , 279 ]. This section will focus on therapeutic applications of EVs as therapeutic targets by blocking their pathological roles, as well as their use as therapeutics by employing their physiological roles.…”

Section: Pharmacology Of Extracellular Vesiclesmentioning

confidence: 99%

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

Al-Jipouri,

Eritja,

Bozic

2023

IJMS

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Extracellular vesicles (EVs) are nanoparticles released from various cell types that have emerged as powerful new therapeutic option for a variety of diseases. EVs are involved in the transmission of biological signals between cells and in the regulation of a variety of biological processes, highlighting them as potential novel targets/platforms for therapeutics intervention and/or delivery. Therefore, it is necessary to investigate new aspects of EVs’ biogenesis, biodistribution, metabolism, and excretion as well as safety/compatibility of both unmodified and engineered EVs upon administration in different pharmaceutical dosage forms and delivery systems. In this review, we summarize the current knowledge of essential physiological and pathological roles of EVs in different organs and organ systems. We provide an overview regarding application of EVs as therapeutic targets, therapeutics, and drug delivery platforms. We also explore various approaches implemented over the years to improve the dosage of specific EV products for different administration routes.

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“…A recent scoping review of registered clinical trials investigating EVs reported that only 6 of the 73 (8%) trials examined provided adequate information on isolation protocols and characterization of EVs, and only 2 trials reported information regarding the size parameters of the EVs used. 8 Furthermore, none of the 49 trials using MSC-derived EVs reported sufficient information to satisfy the minimal criteria for defining MSCs as established by the International Society for Cell & Gene Therapy. 8 Similarly, none of the trials in this review reported sufficient product isolation and characterization information to satisfy the criteria established in the Minimal Information for Studies of Extracellular Vesicles guidelines.…”

Section: Current Clinical Trialsmentioning

confidence: 99%

“…8 Furthermore, none of the 49 trials using MSC-derived EVs reported sufficient information to satisfy the minimal criteria for defining MSCs as established by the International Society for Cell & Gene Therapy. 8 Similarly, none of the trials in this review reported sufficient product isolation and characterization information to satisfy the criteria established in the Minimal Information for Studies of Extracellular Vesicles guidelines. 14 Another challenge is the scaling up of cell cultures for the manufacture of EVs in the numbers required for clinical use.…”

Section: Current Clinical Trialsmentioning

confidence: 99%

Exosomes: The New Kid on the Block in Orthobiologics

Rodeo

2023

Am J Sports Med

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Registered clinical trials investigating treatment with cell-derived extracellular vesicles: a scoping review

Cited by 27 publications

References 29 publications

Extracellular vesicles derived from immortalized human natural killer cell line NK3.3 as a novel therapeutic for multiple myeloma

Extracellular vesicles derived from immortalized human natural killer cell line NK3.3 as a novel therapeutic for multiple myeloma

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

Exosomes: The New Kid on the Block in Orthobiologics

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