Chimeric Antigen Receptor Engineering of Mesenchymal Stromal Cells (CAR-MSC) Enhance Immunosuppression and Outcomes in Graft Versus Host Disease (GvHD) Preclinical Models

Sirpilla, Olivia; Sakemura, Reona; Hefazi, Mehrdad; Girsch, James H.; Huynh, Truc; Cox, Michelle J.; Schick, Kendall J.; Manriquez-Roman, Claudia; Can, İsmail; Yun, Kun; Stewart, Carli M.; Ogbodo, Ekene J.; Siegler, Elizabeth L.; Kenderian, Saad S.

doi:10.1182/blood-2022-158872

Cited by 2 publications

(3 citation statements)

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“…Researchers have begun work on engineering CAR-natural killer, CAR-macrophages, and even CARmesenchymal stromal cells. [135][136][137] It is becoming increasingly apparent that immunotherapy may be the key to producing lasting remission for patients with hematologic malignancy given that the immune system is "living" and has the ability to persist and adapt continuously and dynamically. It may not be presumptuous to think that with continued advances in the field, CAR-T therapy may just be the fabled "magic bullet" that edges us toward a cure for some, if not most, hematologic malignancies.…”

Section: Future Perspectivesmentioning

confidence: 99%

“…These challenges have fueled rapid progress in CAR‐T research which have led to the creation of newer generations of CAR‐T with improved specificity, durability, and more manageable toxicities, as well as numerous opportunities even beyond the T‐cell space. Researchers have begun work on engineering CAR‐natural killer, CAR‐macrophages, and even CAR‐mesenchymal stromal cells 135–137 …”

Section: Future Perspectivesmentioning

confidence: 99%

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Chimeric antigen receptor T‐cell therapy in hematologic malignancies: Successes, challenges, and opportunities

Ho,

Zanwar,

Paludo

2023

European J of Haematology

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The success of chimeric antigen receptor T‐cell (CAR‐T) therapy in hematologic malignancies has realized a longstanding effort toward harnessing the immune system to fight cancer in a truly personalized fashion. Second generation chimeric antigen receptors (CAR) incorporating co‐stimulatory molecules like 4‐1BB or CD28 were able to overcome some of the hindrances with initial CAR constructs resulting in efficacious products. Many second‐generation CAR‐T products have been approved in the treatment of relapsed/refractory hematologic malignancies including multiple myeloma (MM), non‐Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia. However, challenges remain in optimizing the manufacturing, timely access, limiting the toxicity from CAR‐T infusions and improving sustainability of responses derived with CAR‐T therapy. Here, we summarize the clinical trial data leading to approval CAR‐T therapies in MM and NHL, discuss the limitations with current CAR‐T therapy strategies and review emerging strategies for overcoming these limitations.

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Section: Future Perspectivesmentioning

confidence: 99%

Section: Future Perspectivesmentioning

confidence: 99%

Chimeric antigen receptor T‐cell therapy in hematologic malignancies: Successes, challenges, and opportunities

Ho,

Zanwar,

Paludo

2023

European J of Haematology

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“…Ecad. CAR-MSCs with the CD28ζ signaling domain were generated to test the immunosuppressive function [ 135 ]. The antigen-stimulated Ecad.…”

Section: Introductionmentioning

confidence: 99%

The role of MSCs and CAR-MSCs in cellular immunotherapy

Yan

Zhang

2023

Cell Commun Signal

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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. Graphical Abstract

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Chimeric Antigen Receptor Engineering of Mesenchymal Stromal Cells (CAR-MSC) Enhance Immunosuppression and Outcomes in Graft Versus Host Disease (GvHD) Preclinical Models

Cited by 2 publications

References 0 publications

Chimeric antigen receptor T‐cell therapy in hematologic malignancies: Successes, challenges, and opportunities

Chimeric antigen receptor T‐cell therapy in hematologic malignancies: Successes, challenges, and opportunities

The role of MSCs and CAR-MSCs in cellular immunotherapy

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