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Chimeric Antigen Receptors Against Cancers and Autoimmune Diseases
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Chimeric Antigen Receptors Against Cancers and Autoimmune Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 20 July 2025 | Viewed by 6327

Special Issue Editor

Prof. Dr. Niels Schaft

E-Mail Website
Guest Editor
Department of Dermatology, Universitätsklinikum Erlangen, 91054 Erlangen, Germany
Interests: CAR-T cells; melanoma; adoptive cell therapy; cancer vaccination; cancer immunotherapy; solid tumors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The development of chimeric antigen receptors (CARs) has marked a new era in cancer immunotherapy. Tremendous clinical advances have been achieved via the use of CAR-T cells against a variety of cancers both in preclinical studies and in clinical trials, most notably against leukemia, lymphoma, and multiple myeloma; these studies have resulted in the FDA and EMA approval of these CAR-T-cell therapies. Nevertheless, approximately 50% of patients treated with these approved CAR products experience relapse or refractory disease that necessitates salvage strategies. Furthermore, in patients with solid tumors, CAR-T-cell infusions have not yet been able to induce complete and durable remission. Very recently, the clinical efficacy of CAR-T cells was also proven in patients with autoimmune diseases.

Due to the rapid evolution of this field, the aim of this Special Issue is to focus on advancements and novel strategies regarding CARs for the therapy of cancer and autoimmune diseases.  

Prof. Dr. Niels Schaft
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • chimeric antigen receptor (CAR)
  • cancer
  • autoimmune disease
  • solid tumor
  • effector cell
  • CAR format
  • CAR transfer
  • tumor microenvironment
  • targeted antigen

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Published Papers (3 papers)

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Research

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25 pages, 5401 KiB  
Article
Optimal Chimeric Antigen Receptor (CAR)-mRNA for Transient CAR T Cell Generation
by Reni Kitte, Robert Serfling, Ulrich Blache, Claudius Seitz, Selina Schrader, Ulrike Köhl, Stephan Fricke, Christian Bär and U. Sandy Tretbar
Int. J. Mol. Sci. 2025, 26(3), 965; https://doi.org/10.3390/ijms26030965 - 23 Jan 2025
Viewed by 1923
Abstract
Genetically modified T lymphocytes expressing chimeric antigen receptors (CARs) are becoming increasingly important in the treatment of hematologic malignancies and are also intensively being investigated for other diseases such as autoimmune disorders and HIV. Current CAR T cell therapies predominantly use viral transduction [...] Read more.
Genetically modified T lymphocytes expressing chimeric antigen receptors (CARs) are becoming increasingly important in the treatment of hematologic malignancies and are also intensively being investigated for other diseases such as autoimmune disorders and HIV. Current CAR T cell therapies predominantly use viral transduction methods which, despite their efficacy, raise safety concerns related to genomic integration and potentially associated malignancies as well as labor- and cost-intensive manufacturing. Therefore, non-viral gene transfer methods, especially mRNA-based approaches, have attracted research interest due to their transient modification and enhanced safety profile. In this study, the optimization of CAR-mRNA for T cell applications is investigated, focusing on the impact of mRNA modifications, in vitro transcription protocols, and purification techniques on the translation efficiency and immunogenicity of mRNA. Furthermore, the refined CAR-mRNA was used to generate transient CAR T cells from acute myeloid leukemia patient samples, demonstrating efficacy in vitro and proof-of-concept for clinically relevant settings. These results highlight the potential of optimized mRNA to produce transient and safe CAR T cells. Full article
(This article belongs to the Special Issue Chimeric Antigen Receptors Against Cancers and Autoimmune Diseases)
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14 pages, 2595 KiB  
Article
Exploring CAR T-Cell Dynamics: Balancing Potent Cytotoxicity and Controlled Inflammation in CAR T-Cells Derived from Systemic Sclerosis and Myositis Patients
by Janin Dingfelder, Jule Taubmann, Franziska von Heydebrand, Michael Aigner, Christina Bergmann, Johannes Knitza, Soo Park, Joseph K. Cheng, Thomas Van Blarcom, Georg Schett, Andreas Mackensen and Gloria Lutzny-Geier
Int. J. Mol. Sci. 2025, 26(2), 467; https://doi.org/10.3390/ijms26020467 - 8 Jan 2025
Viewed by 1830
Abstract
Systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myositis (IIM) are autoimmune diseases managed with long-term immunosuppressive therapies. Hu19-CD828Z, a fully human anti-CD19 chimeric antigen receptor (CAR) with a CD28 costimulatory domain, is engineered to potently deplete B-cells. In this study, [...] Read more.
Systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myositis (IIM) are autoimmune diseases managed with long-term immunosuppressive therapies. Hu19-CD828Z, a fully human anti-CD19 chimeric antigen receptor (CAR) with a CD28 costimulatory domain, is engineered to potently deplete B-cells. In this study, we manufactured Hu19-CD828Z CAR T-cells from peripheral blood of SLE, IIM, and SSc patients and healthy donors (HDs). CAR-mediated, CD19-specific activity of these cells was evaluated in vitro by assessing cytotoxicity, cytokine release, and proliferation assays in response to autologous CD19+ B-cells, the CD19+ NALM-6 B-cell line, or a CD19− U937 non-B-cell line as targets. The results demonstrated an increased proliferation of Hu19-CD828Z CAR T-cells and dose-dependent cytotoxicity against primary autologous and NALM-6 B-cells compared to non-transduced controls or co-cultures with non-B-cells. Notably, autoimmune-patient-derived CAR T-cells produced lower levels of inflammatory cytokines than healthy-donor-derived CAR T-cells in response to CD19+ B-cell targets. These data support the potential of Hu19-CD828Z and its therapeutic cell product KYV-101 as a therapeutic strategy to achieve deep B-cell depletion in SLE, IIM, and SSc patients, and highlights its promise for broader application in B-cell-driven autoimmune disorders. Full article
(This article belongs to the Special Issue Chimeric Antigen Receptors Against Cancers and Autoimmune Diseases)
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Review

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24 pages, 2006 KiB  
Review
Current Non-Viral-Based Strategies to Manufacture CAR-T Cells
by Leon Gehrke, Vasco Dos Reis Gonçalves, Dominik Andrae, Tamas Rasko, Patrick Ho, Hermann Einsele, Michael Hudecek and Sabrina R. Friedel
Int. J. Mol. Sci. 2024, 25(24), 13685; https://doi.org/10.3390/ijms252413685 - 21 Dec 2024
Cited by 1 | Viewed by 1971
Abstract
The successful application of CAR-T cells in the treatment of hematologic malignancies has fundamentally changed cancer therapy. With increasing numbers of registered CAR-T cell clinical trials, efforts are being made to streamline and reduce the costs of CAR-T cell manufacturing while improving their [...] Read more.
The successful application of CAR-T cells in the treatment of hematologic malignancies has fundamentally changed cancer therapy. With increasing numbers of registered CAR-T cell clinical trials, efforts are being made to streamline and reduce the costs of CAR-T cell manufacturing while improving their safety. To date, all approved CAR-T cell products have relied on viral-based gene delivery and genomic integration methods. While viral vectors offer high transfection efficiencies, concerns regarding potential malignant transformation coupled with costly and time-consuming vector manufacturing are constant drivers in the search for cheaper, easier-to-use, safer, and more efficient alternatives. In this review, we examine different non-viral gene transfer methods as alternatives for CAR-T cell production, their advantages and disadvantages, and examples of their applications. Transposon-based gene transfer methods lead to stable but non-targeted gene integration, are easy to handle, and achieve high gene transfer rates. Programmable endonucleases allow targeted integration, reducing the potential risk of integration-mediated malignant transformation of CAR-T cells. Non-integrating CAR-encoding vectors avoid this risk completely and achieve only transient CAR expression. With these promising alternative techniques for gene transfer, all avenues are open to fully exploiting the potential of next-generation CAR-T cell therapy and applying it in a wide range of applications. Full article
(This article belongs to the Special Issue Chimeric Antigen Receptors Against Cancers and Autoimmune Diseases)
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