The role of MSCs and CAR-MSCs in cellular immunotherapy

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Abstract

Chimeric antigen receptors (CARs) are widely used by T cells (CAR-T cells), natural killer cells dendritic cells and macrophages, and they are of great importance in cellular immunotherapy. However, the use of CAR-related products faces several challenges, including the poor persistence of cells carrying CARs, cell dysfunction or exhaustion, relapse of disease, immune effector cell-associated neurotoxicity syndrome, cytokine release syndrome, low efficacy against solid tumors and immunosuppression by the tumor microenvironment. Another important cell therapy regimen involves mesenchymal stem cells (MSCs). Recent studies have shown that MSCs can improve the anticancer functions of CAR-related products. CAR-MSCs can overcome the flaws of cellular immunotherapy. Thus, MSCs can be used as a biological vehicle for CARs. In this review, we first discuss the characteristics and immunomodulatory functions of MSCs. Then, the role of MSCs as a source of exosomes, including the characteristics of MSC-derived exosomes and their immunomodulatory functions, is discussed. The role of MSCs in CAR-related products, CAR-related product-derived exosomes and the effect of MSCs on CAR-related products are reviewed. Finally, the use of MSCs as CAR vehicles is discussed.

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Supplementary Information

The online version contains supplementary material available at 10.1186/s12964-023-01191-4.

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Most cited references 161

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Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

Hadi Valadi, Karin Ekström, Apostolos Bossios … (2007)

Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).

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CAR T cell immunotherapy for human cancer

Michael Milone, Saba Ghassemi, Omkar U Kawalekar … (2018)

Adoptive T cell transfer (ACT) is a new area of transfusion medicine involving the infusion of lymphocytes to mediate antitumor, antiviral, or anti-inflammatory effects. The field has rapidly advanced from a promising form of immuno-oncology in preclinical models to the recent commercial approvals of chimeric antigen receptor (CAR) T cells to treat leukemia and lymphoma. This Review describes opportunities and challenges for entering mainstream oncology that presently face the CAR T field, with a focus on the challenges that have emerged over the past several years.

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Regulation of immune responses by extracellular vesicles.

Paul Robbins, Adrian Morelli (2014)

Extracellular vesicles, including exosomes, are small membrane vesicles derived from multivesicular bodies or from the plasma membrane. Most, if not all, cell types release extracellular vesicles, which then enter the bodily fluids. These vesicles contain a subset of proteins, lipids and nucleic acids that are derived from the parent cell. It is thought that extracellular vesicles have important roles in intercellular communication, both locally and systemically, as they transfer their contents, including proteins, lipids and RNAs, between cells. Extracellular vesicles are involved in numerous physiological processes, and vesicles from both non-immune and immune cells have important roles in immune regulation. Moreover, extracellular vesicle-based therapeutics are being developed and clinically tested for the treatment of inflammatory diseases, autoimmune disorders and cancer. Given the tremendous therapeutic potential of extracellular vesicles, this Review focuses on their role in modulating immune responses, as well as their potential therapeutic applications.

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Author and article information

Contributors

Cheng Zhang: chzhang2014@163.com

Journal

Journal ID (nlm-ta): Cell Commun Signal

Journal ID (iso-abbrev): Cell Commun Signal

Title: Cell Communication and Signaling : CCS

Publisher: BioMed Central (London )

ISSN (Electronic): 1478-811X

Publication date (Electronic): 1 August 2023

Publication date PMC-release: 1 August 2023

Publication date Collection: 2023

Volume: 21

Electronic Location Identifier: 187

Affiliations

GRID grid.417298.1, ISNI 0000 0004 1762 4928, Medical Center of Hematology, State Key Laboratory of Trauma, Burn and Combined Injury, , Xinqiao Hospital, Army Medical University, ; Chongqing, 400037 China

Article

Publisher ID: 1191

DOI: 10.1186/s12964-023-01191-4

PMC ID: 10391838

PubMed ID: 37528472

SO-VID: d3a588f8-dd78-4ca8-917a-eb6aef4dfef6

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 23 April 2023

Date accepted : 7 June 2023

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 82170212

Award Recipient : Cheng Zhang

Funded by: Key Foundation of Joint Project of Chongqing Health Commission and Science and Technology Bureau

Award ID: 2019ZDXM001

Award Recipient : Cheng Zhang

Custom metadata

ScienceOpen disciplines: Cell biology

Keywords: mesenchymal stem cell,car,car-t cells,car-nk cells,car-ms,car-dcs,exosome,immunomodulation,immunotherapy

Data availability:

ScienceOpen disciplines: Cell biology

Keywords: mesenchymal stem cell, car, car-t cells, car-nk cells, car-ms, car-dcs, exosome, immunomodulation, immunotherapy

The role of MSCs and CAR-MSCs in cellular immunotherapy

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Abstract

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Supplementary Information

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Most cited references 161

Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

CAR T cell immunotherapy for human cancer

Regulation of immune responses by extracellular vesicles.

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