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Cells
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CAR T Cells: A Road Trip to Tumor Elimination
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CAR T Cells: A Road Trip to Tumor Elimination

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

Deadline for manuscript submissions: closed (15 September 2023) | Viewed by 7833

Special Issue Editor

Dr. Beatriz Martín-Antonio

E-Mail Website1 Website2
Guest Editor
Instituto de Investigación Sanitaria/Fundación Jiménez Diaz, Madrid, Spain
Interests: anti-tumor activity; cancer research; cell biology; immunology; natural killer cells

Special Issue Information

Dear Colleagues,

CAR-T cell treatment has modified the concept of treatment for hematological malignancies in the last decade. Compared to traditional chemotherapy treatments, CAR-T cell treatment avoids the toxicities associated with continuous chemotherapy treatments, thereby improving patients' quality of life. Clinical results in pediatric patients with acute lymphoblastic leukemia have demonstrated maintained responses over the years due to the persistence of the CAR-T cells. However, in elderly cancer patients with hematological malignancies, CAR-T cells’ persistence is of shorter duration due, among other factors, to an aged immune system with immunosenescent T cells. Moreover, in solid tumors, CAR-T cells face barriers, such as those promoted by the tumor microenvironment, which decreases their efficacy. In addition, the presence of a heterogeneous mixture of cells in solid tumors and the lack of highly specific targets in this context decrease CAR-T cells' efficacy and lead to enhanced toxicities. In this regard, novel CAR constructs are being designed to avoid these problems. For instance, CAR-T cell activity can be modulated to prevent toxicities, and the CAR construct can be equipped with molecules that are secreted to fight the tumor microenvironment. Moreover, allogeneic universal CAR-T cells are being designed to decrease the costs associated with this therapy and obtain healthier CAR-T cells than those from cancer patients. Eventually, all these improvements are expected to improve the efficacy and safety of CAR-T cells in solid tumors and elderly cancer patients to achieve outstanding responses such as those obtained in pediatric acute lymphoblastic leukemia patients. This Special Issue offers an Open Access forum that aims to bring together a collection of original research and review articles addressing the main problems associated with this therapy and strategies to solve them in elderly patients with hematological malignancies and solid tumors.

We hope to provide stimulating literature for this growing field of immunotherapy. Suggested potential topics may include T cell immunosenescence; tumor microenvironment; modulation of CAR-T cell activity; CAR-T cell specificity; CAR-T cell efficacy; universal CAR-T cells, novel CAR constructs; neurotoxicity; cytokine release syndrome; on-target off-tumor toxicity.

Dr. Beatriz Martín-Antonio
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. 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

  • CAR T cells
  • immunotherapy
  • cancer treatment
  • tumor elimination
  • chimeric antigen receptor
  • cellular therapy
  • tumor targeting
  • oncology
  • tumor immunology
  • CAR-T cell therapy

Published Papers (3 papers)

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Review

20 pages, 3360 KiB  
Review
Chimeric Antigen Receptor T-Cell Therapy and Hematopoiesis
by Bryanna Reinhardt, Patrick Lee and Joshua P. Sasine
Cells 2023, 12(4), 531; https://doi.org/10.3390/cells12040531 - 07 Feb 2023
Cited by 1 | Viewed by 2415
Abstract
Chimeric Antigen Receptor (CAR) T-cell therapy is a promising treatment option for patients suffering from B-cell- and plasma cell-derived hematologic malignancies and is being adapted for the treatment of solid cancers. However, CAR T is associated with frequently severe toxicities such as cytokine [...] Read more.
Chimeric Antigen Receptor (CAR) T-cell therapy is a promising treatment option for patients suffering from B-cell- and plasma cell-derived hematologic malignancies and is being adapted for the treatment of solid cancers. However, CAR T is associated with frequently severe toxicities such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), macrophage activation syndrome (MAS), and prolonged cytopenias—a reduction in the number of mature blood cells of one or more lineage. Although we understand some drivers of these toxicities, their mechanisms remain under investigation. Since the CAR T regimen is a complex, multi-step process with frequent adverse events, ways to improve the benefit-to-risk ratio are needed. In this review, we discuss a variety of potential solutions being investigated to address the limitations of CAR T. First, we discuss the incidence and characteristics of CAR T-related cytopenias and their association with reduced CAR T-cell efficacy. We review approaches to managing or mitigating cytopenias during the CAR T regimen—including the use of growth factors, allogeneic rescue, autologous hematopoietic stem cell infusion, and alternative conditioning regimens. Finally, we introduce novel methods to improve CAR T-cell-infusion products and the implications of CAR T and clonal hematopoiesis. Full article
(This article belongs to the Special Issue CAR T Cells: A Road Trip to Tumor Elimination)
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12 pages, 1329 KiB  
Review
The Intracellular Proteome as a Source for Novel Targets in CAR-T and T-Cell Engagers-Based Immunotherapy
by Inbar Arman, Maya Haus-Cohen and Yoram Reiter
Cells 2023, 12(1), 27; https://doi.org/10.3390/cells12010027 - 21 Dec 2022
Cited by 2 | Viewed by 2490
Abstract
The impressive clinical success of cancer immunotherapy has motivated the continued search for new targets that may serve to guide potent effector functions in an attempt to efficiently kill malignant cells. The intracellular proteome is an interesting source for such new targets, such [...] Read more.
The impressive clinical success of cancer immunotherapy has motivated the continued search for new targets that may serve to guide potent effector functions in an attempt to efficiently kill malignant cells. The intracellular proteome is an interesting source for such new targets, such as neo-antigens and others, with growing interest in their application for cell-based immunotherapies. These intracellular-derived targets are peptides presented by MHC class I molecules on the cell surface of malignant cells. These disease-specific class I HLA–peptide complexes can be targeted by specific TCRs or by antibodies that mimic TCR-specificity, termed TCR-like (TCRL) antibodies. Adoptive cell transfer of TCR engineered T cells and T-cell-receptor-like based CAR-T cells, targeted against a peptide-MHC of interest, are currently tested as cancer therapeutic agents in pre-clinical and clinical trials, along with soluble TCR- and TCRL-based agents, such as immunotoxins and bi-specific T cell engagers. Targeting the intracellular proteome using TCRL- and TCR-based molecules shows promising results in cancer immunotherapy, as exemplified by the success of the anti-gp100/HLA-A2 TCR-based T cell engager, recently approved by the FDA for the treatment of unresectable or metastatic uveal melanoma. This review is focused on the selection and isolation processes of TCR- and TCRL-based targeting moieties, with a spotlight on pre-clinical and clinical studies, examining peptide-MHC targeting agents in cancer immunotherapy. Full article
(This article belongs to the Special Issue CAR T Cells: A Road Trip to Tumor Elimination)
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23 pages, 1047 KiB  
Review
Harnessing the Potential of Chimeric Antigen Receptor T-Cell Therapy for the Treatment of T-Cell Malignancies: A Dare or Double Dare?
by Rita Assi and Huda Salman
Cells 2022, 11(24), 3971; https://doi.org/10.3390/cells11243971 - 08 Dec 2022
Cited by 2 | Viewed by 2184
Abstract
Historical standard of care treatments of T-cell malignancies generally entailed the use of cytotoxic and depleting approaches. These strategies are, however, poorly validated and record dismal long-term outcomes. More recently, the introduction and approval of chimeric antigen receptor (CAR)-T cell therapy has revolutionized [...] Read more.
Historical standard of care treatments of T-cell malignancies generally entailed the use of cytotoxic and depleting approaches. These strategies are, however, poorly validated and record dismal long-term outcomes. More recently, the introduction and approval of chimeric antigen receptor (CAR)-T cell therapy has revolutionized the therapy of B-cell malignancies. Translating this success to the T-cell compartment has so far proven hazardous, entangled by risks of fratricide, T-cell aplasia, and product contamination by malignant cells. Several strategies have been utilized to overcome these challenges. These include the targeting of a selective cognate antigen exclusive to T-cells or a subset of T-cells, disruption of target antigen expression on CAR-T constructs, use of safety switches, non-viral transduction, and the introduction of allogeneic compounds and gene editing technologies. We herein overview these historical challenges and revisit the opportunities provided as potential solutions. An in-depth understanding of the tumor microenvironment is required to optimally harness the potential of the immune system to treat T-cell malignancies. Full article
(This article belongs to the Special Issue CAR T Cells: A Road Trip to Tumor Elimination)
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