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Cancers
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Innovative Immunotherapies: CAR-T Cell Therapy for Cancers
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Innovative Immunotherapies: CAR-T Cell Therapy for Cancers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: 13 December 2024 | Viewed by 12586

Special Issue Editor

Dr. Shebli Atrash

E-Mail Website
Guest Editor
Levine Cancer Institute, Charlotte, NC 28204, USA
Interests: plasma cell disorders; multiple myeloma; amyloidosis; plasma cell leukemia; CAR-T
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Immunotherapy harnesses the power of the immune system to recognize and attack cancer cells. Innovative immunotherapies, such as CAR-T, have shown advantageous outcomes in various cancer types. By modifying a patient's T cells, CAR-T targets specific antigens in the cancer cells. This precision targeting allows for a particular attack on cancer cells while minimizing damage to healthy cells. However, it is important to note that CAR-T therapy has some encumbrances and challenges. For example, it can be associated with significant side effects, including cytokine release syndrome and neurotoxicity. Improving CAR-T involves better target selection, higher potency, longer persistency, and overcoming resistance mechanisms that are employed by the cancer cells to evade/escape the immune system. In this Special Issue, we will encourage novel approaches and perspectives of CAR-T cell therapy for cancers.

Dr. Shebli Atrash
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 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. Cancers 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 2900 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

  • CAR-T
  • NK-CAR
  • immunotherapy
  • cancer
  • resistance mechanisms

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Published Papers (4 papers)

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Research

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19 pages, 4056 KiB  
Article
Optimizing Ex Vivo CAR-T Cell-Mediated Cytotoxicity Assay through Multimodality Imaging
by John G. Foulke, Luping Chen, Hyeyoun Chang, Catherine E. McManus, Fang Tian and Zhizhan Gu
Cancers 2024, 16(14), 2497; https://doi.org/10.3390/cancers16142497 - 9 Jul 2024
Viewed by 1808
Abstract
CAR-T cell-based therapies have demonstrated remarkable efficacy in treating malignant cancers, especially liquid tumors, and are increasingly being evaluated in clinical trials for solid tumors. With the FDA’s initiative to advance alternative methods for drug discovery and development, full human ex vivo assays [...] Read more.
CAR-T cell-based therapies have demonstrated remarkable efficacy in treating malignant cancers, especially liquid tumors, and are increasingly being evaluated in clinical trials for solid tumors. With the FDA’s initiative to advance alternative methods for drug discovery and development, full human ex vivo assays are increasingly essential for precision CAR-T development. However, prevailing ex vivo CAR-T cell-mediated cytotoxicity assays are limited by their use of radioactive materials, lack of real-time measurement, low throughput, and inability to automate, among others. To address these limitations, we optimized the assay using multimodality imaging methods, including bioluminescence, impedance tracking, phase contrast, and fluorescence, to track CAR-T cells co-cultured with CD19, CD20, and HER2 luciferase reporter cancer cells in real-time. Additionally, we varied the ratio of CAR-T cells to cancer cells to determine optimal cytotoxicity readouts. Our findings demonstrated that the CAR-T cell group effectively attacked cancer cells, and the optimized assay provided superior temporal and spatial precision measurements of ex vivo CAR-T killing of cancer cells, confirming the reliability, consistency, and high throughput of the optimized assay. Full article
(This article belongs to the Special Issue Innovative Immunotherapies: CAR-T Cell Therapy for Cancers)
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21 pages, 4413 KiB  
Article
Preclinical Evaluation of Novel Folate Receptor 1-Directed CAR T Cells for Ovarian Cancer
by Julie Daigre, Manuel Martinez-Osuna, Maria Bethke, Larissa Steiner, Vera Dittmer, Katrin Krischer, Cathrin Bleilevens, Janina Brauner, Jens Kopatz, Matthias David Grundmann, Paurush Praveen, Dominik Eckardt, Andreas Bosio and Christoph Herbel
Cancers 2024, 16(2), 333; https://doi.org/10.3390/cancers16020333 - 12 Jan 2024
Cited by 4 | Viewed by 4436
Abstract
Treatment options for ovarian cancer patients are limited, and a high unmet clinical need remains for targeted and long-lasting, efficient drugs. Genetically modified T cells expressing chimeric antigen receptors (CAR), are promising new drugs that can be directed towards a defined target and [...] Read more.
Treatment options for ovarian cancer patients are limited, and a high unmet clinical need remains for targeted and long-lasting, efficient drugs. Genetically modified T cells expressing chimeric antigen receptors (CAR), are promising new drugs that can be directed towards a defined target and have shown efficient, as well as persisting, anti-tumor responses in many patients. We sought to develop novel CAR T cells targeting ovarian cancer and to assess these candidates preclinically. First, we identified potential CAR targets on ovarian cancer samples. We confirmed high and consistent expressions of the tumor-associated antigen FOLR1 on primary ovarian cancer samples. Subsequently, we designed a series of CAR T cell candidates against the identified target and demonstrated their functionality against ovarian cancer cell lines in vitro and in an in vivo xenograft model. Finally, we performed additional in vitro assays recapitulating immune suppressive mechanisms present in solid tumors and developed a process for the automated manufacturing of our CAR T cell candidate. These findings demonstrate the feasibility of anti-FOLR1 CAR T cells for ovarian cancer and potentially other FOLR1-expressing tumors. Full article
(This article belongs to the Special Issue Innovative Immunotherapies: CAR-T Cell Therapy for Cancers)
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Review

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24 pages, 1403 KiB  
Review
Advancement and Challenges in Monitoring of CAR-T Cell Therapy: A Comprehensive Review of Parameters and Markers in Hematological Malignancies
by Weronika Ploch, Karol Sadowski, Wioletta Olejarz and Grzegorz W. Basak
Cancers 2024, 16(19), 3339; https://doi.org/10.3390/cancers16193339 - 29 Sep 2024
Viewed by 2048
Abstract
Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment for relapsed/refractory B-cell lymphomas. Despite its success, this therapy is accompanied by a significant frequency of adverse events, including cytokine release syndrome (CRS), immune-effector-cell-associated neurotoxicity syndrome (ICANS), or cytopenias, reaching even up to [...] Read more.
Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment for relapsed/refractory B-cell lymphomas. Despite its success, this therapy is accompanied by a significant frequency of adverse events, including cytokine release syndrome (CRS), immune-effector-cell-associated neurotoxicity syndrome (ICANS), or cytopenias, reaching even up to 80% of patients following CAR-T cell therapy. CRS results from the uncontrolled overproduction of proinflammatory cytokines, which leads to symptoms such as fever, headache, hypoxia, or neurological complications. CAR-T cell detection is possible by the use of flow cytometry (FC) or quantitative polymerase chain reaction (qPCR) assays, the two primary techniques used for CAR-T evaluation in peripheral blood, bone marrow (BM), and cerebrospinal fluid (CSF). State-of-the-art imaging technologies play a crucial role in monitoring the distribution and persistence of CAR-T cells in clinical trials. Still, they can also be extended with the use of FC and digital PCR (dPCR). Monitoring the changes in cell populations during disease progression and treatment gives an important insight into how the response to CAR-T cell therapy develops on a cellular level. It can help improve the therapeutic design and optimize CAR-T cell therapy to make it more precise and personalized, which is crucial to overcoming the problem of tumor relapse. Full article
(This article belongs to the Special Issue Innovative Immunotherapies: CAR-T Cell Therapy for Cancers)
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29 pages, 775 KiB  
Review
Chimeric Antigen Receptor (CAR) T-Cell Therapy in Hematologic Malignancies: Clinical Implications and Limitations
by Philipp Blüm and Sabine Kayser
Cancers 2024, 16(8), 1599; https://doi.org/10.3390/cancers16081599 - 22 Apr 2024
Cited by 3 | Viewed by 3479
Abstract
Chimeric antigen receptor (CAR) T-cell therapy has become a powerful treatment option in B-cell and plasma cell malignancies, and many patients have benefited from its use. To date, six CAR T-cell products have been approved by the FDA and EMA, and many more [...] Read more.
Chimeric antigen receptor (CAR) T-cell therapy has become a powerful treatment option in B-cell and plasma cell malignancies, and many patients have benefited from its use. To date, six CAR T-cell products have been approved by the FDA and EMA, and many more are being developed and investigated in clinical trials. The whole field of adoptive cell transfer has experienced an unbelievable development process, and we are now at the edge of a new era of immune therapies that will have its impact beyond hematologic malignancies. Areas of interest are, e.g., solid oncology, autoimmune diseases, infectious diseases, and others. Although much has been achieved so far, there is still a huge effort needed to overcome significant challenges and difficulties. We are witnessing a rapid expansion of knowledge, induced by new biomedical technologies and CAR designs. The era of CAR T-cell therapy has just begun, and new products will widen the therapeutic landscape in the future. This review provides a comprehensive overview of the clinical applications of CAR T-cells, focusing on the approved products and emphasizing their benefits but also indicating limitations and challenges. Full article
(This article belongs to the Special Issue Innovative Immunotherapies: CAR-T Cell Therapy for Cancers)
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