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Biomedicines
Special Issues
Roles of T Cells in Immunotherapy
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Roles of T Cells in Immunotherapy

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 11064

Special Issue Editors

Dr. Zhan Zhou

E-Mail Website
Guest Editor
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
Interests: AI-driven drug discovery; pharmaceutical biotechnology; pharmacogenomics; neoantigens; computational biology
Special Issues, Collections and Topics in MDPI journals
Dr. Wenbin Zhao

E-Mail Website
Guest Editor
Zhejiang University Innovation Institute for Artificial Intelligence in Medicine, Hangzhou 310018, China
Interests: tumor immunotherapies; T-cell receptors; T-cell engagers; antibody–drug conjugates; neoantigens
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tumor immunotherapies have achieved important success, but they still have some problems, such as low effective rate and unclear effectiveness. As important effector cells of human immunity, T cells are directly or indirectly involved in tumor immunotherapies. Therefore, in-depth analysis of the roles of T cells in different immunotherapies is an effective way to improve their clinical efficacy. In this Special Issue, we welcome the submission of original research papers and reviews on the roles of T cells in immunotherapy. Relevant topics of interest to this Special Issue include (but are not limited to):

  • Recognition of T-cell epitopes or tumor neoantigens;
  • Design of tumor vaccines;
  • T-cell antigen recognition;
  • Design of TCR-based immunotherapies;
  • Regulation of T-cell activities.

Dr. Zhan Zhou
Dr. Wenbin Zhao
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. Biomedicines 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 2600 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

  • tumor immunotherapies
  • T-cell engagers
  • adoptive T-cell therapy
  • immune checkpoint inhibitors
  • tumor vaccines
  • costimulatory signal
  • T-cell receptors
  • neoantigens

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Published Papers (5 papers)

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Research

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11 pages, 2757 KiB  
Article
Evaluation of Anti-CAR Linker mAbs for CAR T Monitoring after BiTEs/bsAbs and CAR T-Cell Pretreatment
by Anja Grahnert, Sabine Seiffert, Kerstin Wenk, Dominik Schmiedel, Andreas Boldt, Vladan Vucinic, Maximilian Merz, Uwe Platzbecker, Christian Klemann, Ulrike Koehl and Maik Friedrich
Biomedicines 2024, 12(8), 1641; https://doi.org/10.3390/biomedicines12081641 - 24 Jul 2024
Viewed by 1303
Abstract
For the monitoring of chimeric antigen receptor (CAR) T-cell therapies, antigen-based CAR detection methods are usually applied. However, for each target-antigen, a separate detection system is required. Furthermore, when monitored CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell [...] Read more.
For the monitoring of chimeric antigen receptor (CAR) T-cell therapies, antigen-based CAR detection methods are usually applied. However, for each target-antigen, a separate detection system is required. Furthermore, when monitored CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods produce false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment promise a universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19-targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel, the sensitivity was significantly lower compared to that for antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel, or Ide-cel, respectively. Cilta-cel (containing a monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but are not universally applicable. Full article
(This article belongs to the Special Issue Roles of T Cells in Immunotherapy)
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12 pages, 1927 KiB  
Article
T Cell Receptor-Directed Bispecific T Cell Engager Targeting MHC-Linked NY-ESO-1 for Tumor Immunotherapy
by Yiming Li, Wenbin Zhao, Ying Shen, Yingchun Xu, Shuqing Chen and Liqiang Pan
Biomedicines 2024, 12(4), 776; https://doi.org/10.3390/biomedicines12040776 - 1 Apr 2024
Cited by 1 | Viewed by 2973
Abstract
Antibody-based bispecific T cell engagers (TCEs) that redirect T cells to kill tumor cells have shown a promising therapeutic effect on hematologic malignancies. However, tumor-specific targeting is still a challenge for TCEs, impeding the development of TCEs for solid tumor therapy. The major [...] Read more.
Antibody-based bispecific T cell engagers (TCEs) that redirect T cells to kill tumor cells have shown a promising therapeutic effect on hematologic malignancies. However, tumor-specific targeting is still a challenge for TCEs, impeding the development of TCEs for solid tumor therapy. The major histocompatibility complex (MHC) presents almost all intracellular peptides (including tumor-specific peptides) on the cell surface to be scanned by the TCR on T cells. With the premise of choosing optimal peptides, the final complex peptide–MHC could be the tumor-specific target for TCEs. Here, a novel TCR-directed format of a TCE targeting peptide–MHC was designed named IgG-T-TCE, which was modified from the IgG backbone and prepared in a mammalian cell expression system. The recombinant IgG-T-TCE-NY targeting NY-ESO-1157–165/HLA-A*02:01 could be generated in HEK293 cells with a glycosylated TCR and showed potency in T cell activation and redirecting T cells to specifically kill target tumor cells. We also found that the in vitro activity of IgG-T-TCE-NY could be leveraged by various anti-CD3 antibodies and Fc silencing. The IgG-T-TCE-NY efficiently inhibited tumor growth in a tumor–PBMC co-engrafted mouse model without any obvious toxicities. Full article
(This article belongs to the Special Issue Roles of T Cells in Immunotherapy)
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20 pages, 4692 KiB  
Article
Mice Generated with Induced Pluripotent Stem Cells Derived from Mucosal-Associated Invariant T Cells
by Chie Sugimoto, Hiroyoshi Fujita and Hiroshi Wakao
Biomedicines 2024, 12(1), 137; https://doi.org/10.3390/biomedicines12010137 - 9 Jan 2024
Cited by 2 | Viewed by 1485
Abstract
The function of mucosal-associated invariant T (MAIT) cells, a burgeoning member of innate-like T cells abundant in humans and implicated in many diseases, remains obscure. To explore this, mice with a rearranged T cell receptor (TCR) α or β locus, specific for MAIT [...] Read more.
The function of mucosal-associated invariant T (MAIT) cells, a burgeoning member of innate-like T cells abundant in humans and implicated in many diseases, remains obscure. To explore this, mice with a rearranged T cell receptor (TCR) α or β locus, specific for MAIT cells, were generated via induced pluripotent stem cells derived from MAIT cells and were designated Vα19 and Vβ8 mice, respectively. Both groups of mice expressed large numbers of MAIT cells. The MAIT cells from these mice were activated by cytokines and an agonist to produce IFN-γ and IL-17. While Vβ8 mice showed resistance in a cancer metastasis model, Vα19 mice did not. Adoptive transfer of MAIT cells from the latter into the control mice, however, recapitulated the resistance. These mice present an implication for understanding the role of MAIT cells in health and disease and in developing treatments for the plethora of diseases in which MAIT cells are implicated. Full article
(This article belongs to the Special Issue Roles of T Cells in Immunotherapy)
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22 pages, 7294 KiB  
Article
Evaluation of CAR-T Cells’ Cytotoxicity against Modified Solid Tumor Cell Lines
by Aigul Kh. Valiullina, Ekaterina A. Zmievskaya, Irina A. Ganeeva, Margarita N. Zhuravleva, Ekaterina E. Garanina, Albert A. Rizvanov, Alexey V. Petukhov and Emil R. Bulatov
Biomedicines 2023, 11(2), 626; https://doi.org/10.3390/biomedicines11020626 - 19 Feb 2023
Cited by 27 | Viewed by 3399
Abstract
In recent years, adoptive cell therapy has gained a new perspective of application due to the development of technologies and the successful clinical use of CAR-T cells for the treatment of patients with malignant B-cell neoplasms. However, the efficacy of CAR-T therapy against [...] Read more.
In recent years, adoptive cell therapy has gained a new perspective of application due to the development of technologies and the successful clinical use of CAR-T cells for the treatment of patients with malignant B-cell neoplasms. However, the efficacy of CAR-T therapy against solid tumor remains a major scientific and clinical challenge. In this work, we evaluated the cytotoxicity of 2nd generation CAR-T cells against modified solid tumors cell lines—lung adenocarcinoma cell line H522, prostate carcinoma PC-3M, breast carcinoma MDA-MB-231, and epidermoid carcinoma A431 cell lines transduced with lentiviruses encoding red fluorescent protein Katushka2S and the CD19 antigen. A correlation was demonstrated between an increase in the secretion of proinflammatory cytokines and a decrease in the confluence of tumor cells’ monolayer. The proposed approach can potentially be applied to preliminarily assess CAR-T cell efficacy for the treatment of solid tumors and estimate the risks of developing cytokine release syndrome. Full article
(This article belongs to the Special Issue Roles of T Cells in Immunotherapy)
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Review

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17 pages, 330 KiB  
Review
Advancing Allogeneic Hematopoietic Stem Cell Transplantation Outcomes through Immunotherapy: A Comprehensive Review of Optimizing Non-CAR Donor T-Lymphocyte Infusion Strategies
by Stefania Braidotti, Marilena Granzotto, Debora Curci, Barbara Faganel Kotnik and Natalia Maximova
Biomedicines 2024, 12(8), 1853; https://doi.org/10.3390/biomedicines12081853 - 14 Aug 2024
Cited by 1 | Viewed by 1241
Abstract
Optimized use of prophylactic or therapeutic donor lymphocyte infusions (DLI) is aimed at improving clinical outcomes in patients with malignant and non-malignant hematological diseases who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). Memory T-lymphocytes (CD45RA−/CD45RO+) play a crucial role in immune reconstitution [...] Read more.
Optimized use of prophylactic or therapeutic donor lymphocyte infusions (DLI) is aimed at improving clinical outcomes in patients with malignant and non-malignant hematological diseases who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). Memory T-lymphocytes (CD45RA−/CD45RO+) play a crucial role in immune reconstitution post-HSCT. The infusion of memory T cells is proven to be safe and effective in improving outcomes due to the enhanced reconstitution of immunity and increased protection against viremia, without exacerbating graft-versus-host disease (GVHD) risks. Studies indicate their persistence and efficacy in combating viral pathogens, suggesting a viable therapeutic avenue for patients. Conversely, using virus-specific T cells for viremia control presents challenges, such as regulatory hurdles, cost, and production time compared to CD45RA-memory T lymphocytes. Additionally, the modulation of regulatory T cells (Tregs) for therapeutic use has become an important area of investigation in GVHD, playing a pivotal role in immune tolerance modulation, potentially mitigating GVHD and reducing pharmacological immunosuppression requirements. Finally, donor T cell-mediated graft-versus-leukemia immune responses hold promise in curbing relapse rates post-HSCT, providing a multifaceted approach to therapeutic intervention in high-risk disease scenarios. This comprehensive review underscores the multifaceted roles of T lymphocytes in HSCT outcomes and identifies avenues for further research and clinical application. Full article
(This article belongs to the Special Issue Roles of T Cells in Immunotherapy)
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