Extracellular Vesicles Derived from Chimeric Antigen Receptor-T Cells: A Potential Therapy for Cancer

Anat Aharon, Galit Horn, Tali Hana Bar-Lev, Einav Zagagi Yohay, Tova Waks, Maya Levin, Naamit Deshet Unger, Irit Avivi, Anat Globerson Levin

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Chimeric antigen receptor (CAR)-T cells are genetically engineered T cells, directed against a tumor-associated antigen. Extracellular vesicles (EVs) derived from CAR-T cells (CAR-T EVs) may preserve CAR-T activity and overcome one of the major obstacles responsible for CAR-T cell failure in patients with solid tumors. This study aimed to compare CAR-T EVs with their parental cells and explore their cell penetration and cytotoxic activity. Anti-HER-2 CARs were stimulated with specific target cells. EVs were isolated from the cell media and characterized for their content and functions. We found that CAR-T EVs contained a mixture of small and large EVs. Stimulated anti-HER-2+ CAR-T EVs expressed lower cytokine levels compared with their parental CAR-T cells (such as interferon gamma). Higher levels of granzyme B were found in CAR-T EVs (≥20 × ) compared with EVs from unstimulated cells (p < 0.001). Anti-HER-2+ CAR-T EVs bound and penetrated specifically into HER-2 expressing target cells. Similar cytotoxic effects measured by caspase-3/7 activity were found in CAR-T cells and their derived EVs. However, while the CAR-T cells induced massive apoptosis during the first 24 h, CAR-T EVs required 60 - 90 h. In summary, CAR-T EVs provide a novel potent immunotherapy approach that may be effective against solid tumors.

Original languageEnglish
Pages (from-to)1224-1241
Number of pages18
JournalHuman Gene Therapy
Volume32
Issue number19-20
DOIs
StatePublished - Oct 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© Copyright 2021, by Mary Ann Liebert, Inc., publishers 2021.

Keywords

  • CAR-T
  • cancer therapy
  • extravesicles
  • immunotherapy
  • nanotherapy

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