Clinical applications for exosomes: Are we there yet?

Abstract

Exosomes are a subset of extracellular vesicles essential for cell-cell communication in health and disease with the ability to transport nucleic acids, functional proteins and other metabolites. Their clinical use as diagnostic biomarkers and therapeutic carriers has become a major field of research over recent years, generating rapidly expanding scientific interest and financial investment. Their reduced immunogenicity compared to liposomes or viral vectors and their ability to cross major physiological barriers like the blood-brain barrier make them an appealing and innovative option as biomarkers and therapeutic agents. Here, we review the latest clinical developments of exosome biotechnology for diagnostic and therapeutic purposes, including the most recent COVID-19-related exosome-based clinical trials. We present current exosome engineering strategies for optimal clinical safety and efficacy, and assess the technology developed for good manufacturing practice compliant scaling up and storage approaches along with their limitations in pharmaceutical industry.

Keywords: cancer; exosome; immunomodulation; infectious diseases; inflammation; manufacturing; therapeutics.

FIGURE 1

From mode of actions to therapies. Exosomes are promising players where their polymorph uses (orange) can influence their purpose (green) in clinical settings

FIGURE 2

Engineering strategies to refine a specific function and/or tropism to exosomes. Depending on their parent cell line, exosomes can express intrinsic ligands or can be engineered to express specific targeting ligands, stimuli response peptide, fusion protein, immune‐evasive components, or viral glycoproteins. Their cargos can vary from small‐sized genetic material such as noncoding RNAs to components as large as AAV. Exosome engineering can enable specific targeting of the central nervous system, systemic organs, or tumours. AAV: adeno‐associated vector, HEK: human embryonic kidney, MSC: mesenchymal stem cells, PEG: polyethylene glycol, TRAIL: TNF‐related apoptosis‐inducing ligand

FIGURE 3

Exosomes manufacturing for clinical use: from the laboratory to the industry. Schematic highlighting current differences between academic and industrial scale up. Exosomes can be derived from a cell bank or from the patients themselves. Laboratory set up predominantly uses a cell flask platform while the scaling up process involves bioreactors. While bioreactors increase yields and purity, exosomes need to be adequately characterised. FACS: fluorescence‐activated cell sorting, LC/MS: liquid chromatography‐mass spectrometry, MSC: mesenchymal stem cells, ME: microenvironment, NTA: nanoparticle tracking analysis