Emerging Trends in Chimeric Antigen Receptor (CAR)-Based Cellular Immunotherapies

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Cancer Vaccines and Immunotherapy".

Deadline for manuscript submissions: 31 March 2024 | Viewed by 14787

Special Issue Editors

Molecular, Cellular and Developmental Biology Department, University of California Santa Barbara, Santa Barbara, CA 93106, USA
Interests: signal transduction; chimeric antigen receptor; CAR-P; CAR-T; cell therapy; immunotherapy; cell motility; chemotaxis
Special Issues, Collections and Topics in MDPI journals
Department of Surgery, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
Interests: onco-immunology; immunotherapy; immunology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Adoptive cell therapy (ACT) is an advanced approach to cancer treatment in which a patient’s immune cells can be removed, engineered, expanded ex vivo, and transferred back into the patient to boost the anti-tumor immune response. The chimeric antigen receptor T (CAR-T) cell is a form of ACT that has revolutionized treatment for hematological malignancies. So far, the U.S. FDA has approved six CAR-T therapies, and more than 100 companies are currently involved in developing CAR-T-based cellular immunotherapies. However, the success of CAR-T therapy for the treatment of solid tumors remains limited due to (1) antigen heterogeneity in solid tumors, (2) T-cell exhaustion, (3) inability to infiltrate solid tumors, or (4) immunosuppressive tumor microenvironment (TME). In addition, strategies to overcome adverse events (AEs) associated with current CAR-T treatments, such as cytokine release syndrome (CRS), CAR T-cell-related encephalopathy syndrome (CRES), and immune-effector-cell-associated neurotoxicity syndrome (ICANS), are also an active area of investigation.

Hence, there is enormous room for improvement, and efforts are currently underway to design the next generation of CAR-based cellular immunotherapies in various immune-cell types, such as in macrophages (CAR-M or CAR-P), natural killer (NK) cells (CAR-NK), in addition to improving the efficacy of CAR-T cells for solid tumors. The first-in-human CAR-M clinical trial is already in progress for breast cancer treatment. The approaches for streamlining the CAR-M platform for treatment include the generation of allogeneic iPSC-derived CAR-M, CAR monocytes, and optimizing combination therapies.

We invite the submission of original articles and reviews discussing the emerging trends in CAR-based immunotherapies for solid and hematological malignancies, chimeric engulfment receptor (CER) technology, biomarkers for CAR-based therapies, dendritic cell (DC) and regulatory (Treg) T-cell-based immunotherapies, multiplexing CAR, and CAR-based combination therapies. In addition, novel modalities for in vivo CAR therapies (e.g., mRNA-lipid nanoparticles) or pre-clinical investigations are also welcome.

Dr. Abhinava Mishra
Dr. Sandeep Kumar
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. Vaccines is an international peer-reviewed open access monthly 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

  • cancer immunotherapy
  • Adoptive Cell Therapy (ACT)
  • Chimeric Antigen Receptor (CAR)
  • Chimeric Engulfment Receptor (CER)
  • macrophages
  • monocytes
  • NK cells
  • dendritic cells
  • Treg
  • mRNA-lipid nanoparticles

Published Papers (4 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

17 pages, 3888 KiB  
Article
CAR-T Cells with Phytohemagglutinin (PHA) Provide Anti-Cancer Capacity with Better Proliferation, Rejuvenated Effector Memory, and Reduced Exhausted T Cell Frequencies
by Gamze Gulden, Berranur Sert, Tarik Teymur, Yasin Ay, Nulifer Neslihan Tiryaki, Abhinava K. Mishra, Ercument Ovali, Nevzat Tarhan and Cihan Tastan
Vaccines 2023, 11(2), 313; https://doi.org/10.3390/vaccines11020313 - 31 Jan 2023
Cited by 5 | Viewed by 5433
Abstract
The development of genetic modification techniques has led to a new era in cancer treatments that have been limited to conventional treatments such as chemotherapy. intensive efforts are being performed to develop cancer-targeted therapies to avoid the elimination of non-cancerous cells. One of [...] Read more.
The development of genetic modification techniques has led to a new era in cancer treatments that have been limited to conventional treatments such as chemotherapy. intensive efforts are being performed to develop cancer-targeted therapies to avoid the elimination of non-cancerous cells. One of the most promising approaches is genetically modified CAR-T cell therapy. The high central memory T cell (Tcm) and stem cell-like memory T cell (Tscm) ratios in the CAR-T cell population increase the effectiveness of immunotherapy. Therefore, it is important to increase the populations of CAR-expressing Tcm and Tscm cells to ensure that CAR-T cells remain long-term and have cytotoxic (anti-tumor) efficacy. In this study, we aimed to improve CAR-T cell therapy’s time-dependent efficacy and stability, increasing the survival time and reducing the probability of cancer cell growth. To increase the sub-population of Tcm and Tscm in CAR-T cells, we investigated the production of a long-term stable and efficient cytotoxic CAR-T cell by modifications in the cell activation-dependent production using Phytohemagglutinin (PHA). PHA, a lectin that binds to the membranes of T cells and increases metabolic activity and cell division, is studied to increase the Tcm and Tscm population. Although it is known that PHA significantly increases Tcm cells, B-lymphocyte antigen CD19-specific CAR-T cell expansion, its anti-cancer and memory capacity has not yet been tested compared with aCD3/aCD28-amplified CAR-T cells. Two different types of CARs (aCD19 scFv CD8-(CD28 or 4-1BB)-CD3z-EGFRt)-expressing T cells were generated and their immunogenic phenotype, exhausted phenotype, Tcm–Tscm populations, and cytotoxic activities were determined in this study. The proportion of T cell memory phenotype in the CAR-T cell populations generated by PHA was observed to be higher than that of aCD3/aCD28-amplified CAR-T cells with similar and higher proliferation capacity. Here, we show that PHA provides long-term and efficient CAR-T cell production, suggesting a potential alternative to aCD3/aCD28-amplified CAR-T cells. Full article
Show Figures

Figure 1

Review

Jump to: Research, Other

23 pages, 1797 KiB  
Review
CAR-T-Cell Therapy in Multiple Myeloma: B-Cell Maturation Antigen (BCMA) and Beyond
by Abhinava K. Mishra, Ashna Gupta, Gunjan Dagar, Dayasagar Das, Abhijit Chakraborty, Shabirul Haque, Chandra Prakash Prasad, Archana Singh, Ajaz A. Bhat, Muzafar A. Macha, Moez Benali, Kamal S. Saini, Rebecca Ann Previs, Deepak Saini, Dwaipayan Saha, Preyangsee Dutta, Aseem Rai Bhatnagar, Mrinalini Darswal, Abhishek Shankar and Mayank Singh
Vaccines 2023, 11(11), 1721; https://doi.org/10.3390/vaccines11111721 - 16 Nov 2023
Cited by 2 | Viewed by 2801
Abstract
Significant progress has been achieved in the realm of therapeutic interventions for multiple myeloma (MM), leading to transformative shifts in its clinical management. While conventional modalities such as surgery, radiotherapy, and chemotherapy have improved the clinical outcomes, the overarching challenge of effecting a [...] Read more.
Significant progress has been achieved in the realm of therapeutic interventions for multiple myeloma (MM), leading to transformative shifts in its clinical management. While conventional modalities such as surgery, radiotherapy, and chemotherapy have improved the clinical outcomes, the overarching challenge of effecting a comprehensive cure for patients afflicted with relapsed and refractory MM (RRMM) endures. Notably, adoptive cellular therapy, especially chimeric antigen receptor T-cell (CAR-T) therapy, has exhibited efficacy in patients with refractory or resistant B-cell malignancies and is now also being tested in patients with MM. Within this context, the B-cell maturation antigen (BCMA) has emerged as a promising candidate for CAR-T-cell antigen targeting in MM. Alternative targets include SLAMF7, CD38, CD19, the signaling lymphocyte activation molecule CS1, NKG2D, and CD138. Numerous clinical studies have demonstrated the clinical efficacy of these CAR-T-cell therapies, although longitudinal follow-up reveals some degree of antigenic escape. The widespread implementation of CAR-T-cell therapy is encumbered by several barriers, including antigenic evasion, uneven intratumoral infiltration in solid cancers, cytokine release syndrome, neurotoxicity, logistical implementation, and financial burden. This article provides an overview of CAR-T-cell therapy in MM and the utilization of BCMA as the target antigen, as well as an overview of other potential target moieties. Full article
Show Figures

Figure 1

17 pages, 2611 KiB  
Review
CAR T-Cell Immunotherapy Treating T-ALL: Challenges and Opportunities
by Anqi Ren, Xiqin Tong, Na Xu, Tongcun Zhang, Fuling Zhou and Haichuan Zhu
Vaccines 2023, 11(1), 165; https://doi.org/10.3390/vaccines11010165 - 12 Jan 2023
Cited by 9 | Viewed by 3986
Abstract
T-cell acute lymphoblastic leukemia (T-ALL), a form of T-cell malignancy, is a typically aggressive hematological malignancy with high rates of disease relapse and a poor prognosis. Current guidelines do not recommend any specific treatments for these patients, and only allogeneic stem cell transplant, [...] Read more.
T-cell acute lymphoblastic leukemia (T-ALL), a form of T-cell malignancy, is a typically aggressive hematological malignancy with high rates of disease relapse and a poor prognosis. Current guidelines do not recommend any specific treatments for these patients, and only allogeneic stem cell transplant, which is associated with potential risks and toxicities, is a curative therapy. Recent clinical trials showed that immunotherapies, including monoclonal antibodies, checkpoint inhibitors, and CAR T therapies, are successful in treating hematologic malignancies. CAR T cells, which specifically target the B-cell surface antigen CD19, have demonstrated remarkable efficacy in the treatment of B-cell acute leukemia, and some progress has been made in the treatment of other hematologic malignancies. However, the development of CAR T-cell immunotherapy targeting T-cell malignancies appears more challenging due to the potential risks of fratricide, T-cell aplasia, immunosuppression, and product contamination. In this review, we discuss the current status of and challenges related to CAR T-cell immunotherapy for T-ALL and review potential strategies to overcome these limitations. Full article
Show Figures

Figure 1

Other

Jump to: Research, Review

9 pages, 4707 KiB  
Brief Report
T-ALL Cells as Tool Cells for CAR T Therapy
by Anqi Ren, Yuan Zhao and Haichuan Zhu
Vaccines 2023, 11(4), 854; https://doi.org/10.3390/vaccines11040854 - 17 Apr 2023
Cited by 1 | Viewed by 1854
Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is a hematologic malignancy derived from T cells. Numerous CAR T therapies have been successfully applied to treat hematologic malignancies in the clinic. Nevertheless, there remain several challenges to the extensive application of CAR T cell therapy in [...] Read more.
T-cell acute lymphoblastic leukemia (T-ALL) is a hematologic malignancy derived from T cells. Numerous CAR T therapies have been successfully applied to treat hematologic malignancies in the clinic. Nevertheless, there remain several challenges to the extensive application of CAR T cell therapy in T cell malignancies, especially in T-ALL. The main reason for CAR T therapy limitations is that T-ALL cells and normal T cells share antigens, which improves the difficulty of sorting pure T cells, resulting in product contamination, and would lead to CAR T cell fratricide. Thus, we considered creating a CAR on T-ALL tumor cells (CAR T-ALL) to prevent fratricide and eliminate tumor cells. We found that T-ALL cells transduced with CAR would actually commit fratricide. However, CAR T-ALL could kill only tumor cells on T-ALL cell lines, and other types of tumor cells had no killing function after being transferred with CAR. Furthermore, we created CD99 CAR with expression controlled by the Tet-On system on Jurkat cells, which could avoid the fratricide of CAR T-ALL during proliferation, ensuring the controllability of the killing time and effect. Jurkat transduced with a CAR-targeting antigen, which was expressed on other cancer cells, could kill other cancer cell lines, demonstrating that T-ALL cells could be used as tool cells for cancer therapy. Our study supplied a new feasible treatment regimen for cancer treatment in the clinic. Full article
Show Figures

Figure 1

Back to TopTop