CAR-T-Derived Extracellular Vesicles: A Promising Development of CAR-T Anti-Tumor Therapy

Author:

Pagotto Sara12ORCID,Simeone Pasquale23ORCID,Brocco Davide4ORCID,Catitti Giulia23,De Bellis Domenico23ORCID,Vespa Simone23,Di Pietro Natalia12ORCID,Marinelli Lisa4,Di Stefano Antonio4,Veschi Serena4ORCID,De Lellis Laura4ORCID,Verginelli Fabio24ORCID,Kaitsas Francesco5,Iezzi Manuela26ORCID,Pandolfi Assunta12,Visone Rosa12,Tinari Nicola12ORCID,Caruana Ignazio7ORCID,Di Ianni Mauro23ORCID,Cama Alessandro4ORCID,Lanuti Paola23ORCID,Florio Rosalba4ORCID

Affiliation:

1. Department of Medical, Oral and Biotechnological Sciences, “G.d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy

2. Center for Advanced Studies and Technology (CAST), “G.d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy

3. Department of Medicine and Aging Sciences, “G.d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy

4. Department of Pharmacy, “G.d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy

5. Sacred Heart Catholic University, 00168 Rome, Italy

6. Department of Neuroscience, Imaging and Clinical Sciences, “G.d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy

7. Department of Pediatric Haemaology, Oncology and Stem Cell Transplantation, University Hospital Würzburg, 97080 Würzburg, Germany

Abstract

Extracellular vesicles (EVs) are a heterogenous population of plasma membrane-surrounded particles that are released in the extracellular milieu by almost all types of living cells. EVs are key players in intercellular crosstalk, both locally and systemically, given that they deliver their cargoes (consisting of proteins, lipids, mRNAs, miRNAs, and DNA fragments) to target cells, crossing biological barriers. Those mechanisms further trigger a wide range of biological responses. Interestingly, EV phenotypes and cargoes and, therefore, their functions, stem from their specific parental cells. For these reasons, EVs have been proposed as promising candidates for EV-based, cell-free therapies. One of the new frontiers of cell-based immunotherapy for the fight against refractory neoplastic diseases is represented by genetically engineered chimeric antigen receptor T (CAR-T) lymphocytes, which in recent years have demonstrated their effectiveness by reaching commercialization and clinical application for some neoplastic diseases. CAR-T-derived EVs represent a recent promising development of CAR-T immunotherapy approaches. This crosscutting innovative strategy is designed to exploit the advantages of genetically engineered cell-based immunotherapy together with those of cell-free EVs, which in principle might be safer and more efficient in crossing biological and tumor-associated barriers. In this review, we underlined the potential of CAR-T-derived EVs as therapeutic agents in tumors.

Funder

Italian Ministry of University and Research

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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