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Cells
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Potential of CAR-Based Cellular Immunotherapy for Non-oncologic Disorders
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Potential of CAR-Based Cellular Immunotherapy for Non-oncologic Disorders

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 8696

Special Issue Editors

Dr. Györgyi Műzes

E-Mail Website
Guest Editor
Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
Interests: inflammation; cancer; autophagy; carcinogenesis; innate immunity; autoimmune diseases; stem cells
Special Issues, Collections and Topics in MDPI journals
Dr. Ferenc Sipos

E-Mail Website
Guest Editor
Department of Internal Medicine and Hematology, Semmelweis University, Budapest, Hungary
Interests: innate immunity; TLR9-signaling; autophagy; inflammation and cancer; inflammatory bowel disease; colorectal cancer; mucosal regeneration; immunology; gastroenterology; internal medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

As part of cellular immunotherapies of adoptive transfer, the CAR-based options operate with genetically modified T cells that are engineered to express a chimeric antigen receptor (CAR), which is designed to recognize its preset (cognat) antigenic marker on the surface of target cells. This manipulation allows CAR-T cells to deeply affect various pathways of the immune system. Further, the new CAR-derived nanovesicles represent another likely therapeutic alternative. The “living drug” CAR-T therapies have achieved remarkable success in cases of cancer patients especially with relapsed/refractory B cell malignancies. Occasionally, however, serious unique side effects, mainly in the form of cytokine release syndrome and neurotoxicity could occur.

CAR therapy, in general, necessitates the interdependent cooperation of numerous disciplines such as basic immunology, molecular biology, genetic engineering, pharmacology, and clinical science.

According to recent evidence, CAR-modified therapies could also be considered as a promising novel treatment modality for diseases other than cancer. Upon deeper understanding, the underlying immune pathophysiology of different disorders, the exciting CAR concept along with its construction technologies may allow the targeting of various cell and molecular subsets by reprogrammed T cells, and so, improvement of disease outcome.

However, in non-tumorous human disorders, including autoimmune diseases, age-related pathologies due to accumulation of senescent cells, cardiometabolic diseases, inflammatory fibrosis of different tissues and organs, and certain infections (mainly or viral origin), the expected CAR-based approaches are still in early phases; therefore, more detailed research efforts are required for the idea of a widespread clinical application.

The purpose of this Special Issue is to discuss current aspects and challenges of different- generation CAR-based treatment options planned to translate and extend for non-oncologic disorders, from a broad perspective of basic science and clinical practice.

Dr. Györgyi Műzes
Dr. Ferenc Sipos
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • adoptive cell transfer
  • CAR-T cells
  • cell engineering
  • CAR products
  • CAR-T cell therapy
  • non-oncologic disorders
  • autoimmune diseases
  • cardiometabolic diseases
  • inflammatory organ fibrosis
  • senescent cell pathologies
  • infections

Published Papers (3 papers)

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Research

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13 pages, 2858 KiB  
Article
Development of Beta-Amyloid-Specific CAR-Tregs for the Treatment of Alzheimer’s Disease
by Valerie Saetzler, Tobias Riet, Andrea Schienke, Pierre Henschel, Kiara Freitag, Alexander Haake, Frank L. Heppner, Laura Elisa Buitrago-Molina, Fatih Noyan, Elmar Jaeckel and Matthias Hardtke-Wolenski
Cells 2023, 12(16), 2115; https://doi.org/10.3390/cells12162115 - 21 Aug 2023
Cited by 4 | Viewed by 1864
Abstract
Background: Alzheimer’s disease (AD) is a neurodegenerative disease that remains uncured. Its pathogenesis is characterized by the formation of β-amyloid (Aβ) plaques. The use of antigen-specific regulatory T cells (Tregs) through adoptive transfer has shown promise for the treatment of many inflammatory diseases, [...] Read more.
Background: Alzheimer’s disease (AD) is a neurodegenerative disease that remains uncured. Its pathogenesis is characterized by the formation of β-amyloid (Aβ) plaques. The use of antigen-specific regulatory T cells (Tregs) through adoptive transfer has shown promise for the treatment of many inflammatory diseases, although the effectiveness of polyspecific Tregs is limited. Obtaining a sufficient number of antigen-specific Tregs from patients remains challenging. Aims and Methods: To address this problem, we used an antibody-like single-chain variable fragment from a phage library and subsequently generated a chimeric antigen receptor (CAR) targeting β-amyloid. Results: The β-amyloid-specific CARs obtained were stimulated by both recombinant and membrane-bound Aβ isolated from the murine brain. The generated CAR-Tregs showed a normal Treg phenotype, were antigen-specific activatable, and had suppressive capacity. Conclusion: This study highlights the potential of CAR technology to generate antigen-specific Tregs and presents novel approaches for developing functional CARs. Full article
(This article belongs to the Special Issue Potential of CAR-Based Cellular Immunotherapy for Non-oncologic Disorders)
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15 pages, 3171 KiB  
Article
Generation of Chimeric Antigen Receptors against Tetraspanin 7
by Tom Pieper, Kristian Daniel Ralph Roth, Viktor Glaser, Tobias Riet, Laura Elisa Buitrago-Molina, Maike Hagedorn, Maren Lieber, Michael Hust, Fatih Noyan, Elmar Jaeckel and Matthias Hardtke-Wolenski
Cells 2023, 12(11), 1453; https://doi.org/10.3390/cells12111453 - 23 May 2023
Cited by 2 | Viewed by 1771
Abstract
Adoptive transfer of antigen-specific regulatory T cells (Tregs) has shown promising results in the treatment of autoimmune diseases; however, the use of polyspecific Tregs has limited effects. However, obtaining a sufficient number of antigen-specific Tregs from patients with autoimmune disorders remains challenging. Chimeric [...] Read more.
Adoptive transfer of antigen-specific regulatory T cells (Tregs) has shown promising results in the treatment of autoimmune diseases; however, the use of polyspecific Tregs has limited effects. However, obtaining a sufficient number of antigen-specific Tregs from patients with autoimmune disorders remains challenging. Chimeric antigen receptors (CARs) provide an alternative source of T cells for novel immunotherapies that redirect T cells independently of the MHC. In this study, we aimed to generate antibody-like single-chain variable fragments (scFv) and subsequent CARs against tetraspanin 7 (TSPAN7), a membrane protein highly expressed on the surface of pancreatic beta cells, using phage display technology. We established two methods for generating scFvs against TSPAN7 and other target structures. Moreover, we established novel assays to analyze and quantify their binding abilities. The resulting CARs were functional and activated specifically by the target structure, but could not recognize TSPAN7 on the surface of beta cells. Despite this, this study demonstrates that CAR technology is a powerful tool for generating antigen-specific T cells and provides new approaches for generating functional CARs. Full article
(This article belongs to the Special Issue Potential of CAR-Based Cellular Immunotherapy for Non-oncologic Disorders)
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Review

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26 pages, 2319 KiB  
Review
CAR-Based Therapy for Autoimmune Diseases: A Novel Powerful Option
by Györgyi Műzes and Ferenc Sipos
Cells 2023, 12(11), 1534; https://doi.org/10.3390/cells12111534 - 02 Jun 2023
Cited by 3 | Viewed by 4559
Abstract
The pervasive application of chimeric antigen receptor (CAR)-based cellular therapies in the treatment of oncological diseases has long been recognized. However, CAR T cells can target and eliminate autoreactive cells in autoimmune and immune-mediated diseases. By doing so, they can contribute to an [...] Read more.
The pervasive application of chimeric antigen receptor (CAR)-based cellular therapies in the treatment of oncological diseases has long been recognized. However, CAR T cells can target and eliminate autoreactive cells in autoimmune and immune-mediated diseases. By doing so, they can contribute to an effective and relatively long-lasting remission. In turn, CAR Treg interventions may have a highly effective and durable immunomodulatory effect via a direct or bystander effect, which may have a positive impact on the course and prognosis of autoimmune diseases. CAR-based cellular techniques have a complex theoretical foundation and are difficult to implement in practice, but they have a remarkable capacity to suppress the destructive functions of the immune system. This article provides an overview of the numerous CAR-based therapeutic options developed for the treatment of immune-mediated and autoimmune diseases. We believe that well-designed, rigorously tested cellular therapies could provide a promising new personalized treatment strategy for a significant number of patients with immune-mediated disorders. Full article
(This article belongs to the Special Issue Potential of CAR-Based Cellular Immunotherapy for Non-oncologic Disorders)
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