Extracellular vesicles as next generation immunotherapeutics

David W Greening; Rong Xu; Anukreity Ale; Christoph E Hagemeyer; Weisan Chen

doi:10.1016/j.semcancer.2023.02.002

Extracellular vesicles as next generation immunotherapeutics

Semin Cancer Biol. 2023 May:90:73-100. doi: 10.1016/j.semcancer.2023.02.002. Epub 2023 Feb 10.

Authors

David W Greening¹, Rong Xu², Anukreity Ale², Christoph E Hagemeyer², Weisan Chen³

Affiliations

¹ Molecular Proteomics, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Baker Department of Cardiovascular Research, Translation and Implementation, Australia; Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Victoria, Australia; Central Clinical School, Monash University, Victoria, Australia; Baker Department of Cardiometabolic Health, University of Melbourne, Victoria, Australia. Electronic address: david.greening@baker.edu.au.
² Central Clinical School, Monash University, Victoria, Australia; Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
³ Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe University, Victoria, Australia.

PMID: 36773820
DOI: 10.1016/j.semcancer.2023.02.002

Abstract

Extracellular vesicles (EVs) function as a mode of intercellular communication and molecular transfer to elicit diverse biological/functional response. Accumulating evidence has highlighted that EVs from immune, tumour, stromal cells and even bacteria and parasites mediate the communication of various immune cell types to dynamically regulate host immune response. EVs have an innate capacity to evade recognition, transport and transfer functional components to target cells, with subsequent removal by the immune system, where the immunological activities of EVs impact immunoregulation including modulation of antigen presentation and cross-dressing, immune activation, immune suppression, and immune surveillance, impacting the tumour immune microenvironment. In this review, we outline the recent progress of EVs in immunorecognition and therapeutic intervention in cancer, including vaccine and targeted drug delivery and summarise their utility towards clinical translation. We highlight the strategies where EVs (natural and engineered) are being employed as a therapeutic approach for immunogenicity, tumoricidal function, and vaccine development, termed immuno-EVs. With seminal studies providing significant progress in the sequential development of engineered EVs as therapeutic anti-tumour platforms, we now require direct assessment to tune and improve the efficacy of resulting immune responses - essential in their translation into the clinic. We believe such a review could strengthen our understanding of the progress in EV immunobiology and facilitate advances in engineering EVs for the development of novel EV-based immunotherapeutics as a platform for cancer treatment.

Keywords: Cancer; Extracellular vesicles; Immunity; Immunoregulation; Immunosurveillance; Microenvironment; Nanovesicles; Vaccine.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Antigen Presentation
Extracellular Vesicles* / metabolism
Humans
Immunologic Surveillance
Immunotherapy
Neoplasms* / pathology
Tumor Microenvironment