Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper

By T. Lener, M. Gimona, L. Aigner, V. Börger, Edit I. Buzás, G. Camussi, N. Chaput, D. Chatterjee, F. Court, H. D. del Portillo and 46 more. Journal of Extracellular Vesicles, 2015

1,387 citations recorded by the source corpus.

Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/5260259f308b2ad10598b2b68749a200a3373bdb

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Molecular Biology

Citations in the corpus

Exosomes in cancer development, metastasis, and immunity (2019, background): “and further increase cell-specific delivery; 2) how to prevent immune reactions when utilizing nonautologous exosomes, which carry MHC-I or II; 3) how to increase cytotoxic T cell activation when using DC exosomes as a vaccine; 4) how to prolong the half-life of exosome vaccines or bioengineered exo”
Shedding light on the cell biology of extracellular vesicles (2018, neutral): “Several clinical trials involving the use of extracellular vesicle-based delivery are ongoing, for example for the treatment of lung cancer and melanoma, that may become part of an immunotherapy approach that has great potential for patients with advanced cancers 178 .”
Techniques used for the isolation and characterization of extracellular vesicles: results of a worldwide survey (2016, neutral): “The International Society for Extracellular Vesicles (ISEV) has attempted to address some of these issues through the publication of position papers, EV RNA analysis (7) and EV-based therapeutics (8), and the minimal experimental requirements for definition of EVs and their function (MISEV) (5).”
Progress, opportunity, and perspective on exosome isolation - efforts for efficient exosome-based theranostics (2020, background): “In recent years, although several microvesicle markers such as annexin A1 [149], CD29 [150], and Sca1 [151] have been reported, bona fide markers for microvesicle separation are still not available [152].”
Advances in therapeutic applications of extracellular vesicles (2019, background): “Similar to eukaryotic cells, parasites, helminths, fungi, bacteria, and virusinfected cells release EVs (114).”
Extracellular Vesicles: Unique Intercellular Delivery Vehicles. (2017, background): “Their potential for addressability and barrier penetration makes them promising therapeutic delivery vehicles [25].”
Extracellular vesicles in cancer: cell-to-cell mediators of metastasis (2016, background): “Clinically, circulating exosomes and microvesicles isolated from cancer patients have been associated with metastasis or relapse, and therefore could serve as important diagnostic and prognostic markers as well as therapeutic targets (Lener et al., 2015).”