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: 30 June 2024 | Viewed by 5018

Special Issue Editors

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
Interests: AI-driven drug discovery; pharmaceutical biotechnology; pharmacogenomics; neoantigens; computational biology

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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 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

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Keywords

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

Published Papers (3 papers)

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Research

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 - 01 Apr 2024
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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 - 09 Jan 2024
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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 22 | Viewed by 2559
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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