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Boron Neutron Capture Therapy (BNCT) is a new binary radiation therapy for tumor tissue, which kills tumor cells with neutron capture reaction. Boron neutron capture therapy has become a technical means for glioma, melanoma, and other diseases has been included in the clinical backup program. However, BNCT is faced with the key problem of developing and innovating more efficient boron delivery agents to solve the targeting and selectivity. We constructed a tyrosine kinase inhibitor- L -p-boronophenylalanine (TKI-BPA) molecule, aiming to improve the selectivity of boron delivery agents by conjugating targeted drugs while increasing the molecular solubility by adding hydrophilic groups. It shows excellent selectivity in differential uptake of cells, and its solubility is more than 6 times higher than BPA, leading to the saving of boron delivery agents. This modification method is effective for improving the efficiency of the boron delivery agent and is expected to become a potential alternative with high clinical application value., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Zhang, Miao, Zhang, Tang, Teng and Li.)

Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid clonal diseases with diverse clinical courses, and immune dysregulation plays an important role in the pathogenesis of MDS. However, immune dysregulation is complex and heterogeneous in the development of MDS. Lower-risk MDS (LR-MDS) is mainly characterized by immune hyperfunction and increased apoptosis, and the immunosuppressive therapy shows a good response. Instead, higher-risk MDS (HR-MDS) is characterized by immune suppression and immune escape, and the immune activation therapy may improve the survival of HR-MDS. Furthermore, the immune dysregulation of some MDS changes dynamically which is characterized by the coexistence and mutual transformation of immune hyperfunction and immune suppression. Taken together, the authors think that the immune dysregulation in MDS with different risk stratification can be summarized by an advanced philosophical thought "Yin-Yang theory" in ancient China, meaning that the opposing forces may actually be interdependent and interconvertible. Clarifying the mechanism of immune dysregulation in MDS with different risk stratification can provide the new basis for diagnosis and clinical treatment. This review focuses on the manifestations and roles of immune dysregulation in the different risk MDS, and summarizes the latest progress of immunotherapy in MDS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Peng, Zhu, Di, Tang, Guo, Liu, Bai, Li, Li and Zhang.)

Boron neutron capture therapy (BNCT), a cellular-level particle radiation therapy, combines boron compounds selectively delivered to tumor tissue with neutron irradiation. Boronophenylalanine (BPA) is a boron compound widely used in malignant melanoma, malignant brain tumors, and recurrent head and neck cancer. However, neither basic nor clinical research was reported for the treatment of gastric cancer using BPA. Selective distribution of boron in tumors rather than that in blood or normal tissue prior to neutron irradiation is required for the successful treatment of BNCT. This study evaluated the pharmacokinetics and safety of 10 B-labeled BPA ( 10 B-BPA, abbreviated as BPA) and its uptakes in gastric cancer. Pharmacokinetics and safety were evaluated in Sprague-Dawley (SD) rats intravenously injected with BPA. The uptakes of boron in gastric cancer cell line MKN45 and in cell-derived xenografts (CDX) and patient-derived xenografts (PDX) animal models were measured. The results showed that the boron concentration in the blood of rats decreased fast in the first 30 min followed by a steady decrease following the observation time, having a half-life of 44.11 ± 8.90 min and an AUC-last of 815.05 ± 62.09 min×μg/ml. The distribution of boron in different tissues (heart, liver, lung, stomach, and small intestine) of rats revealed a similar pattern in blood except for that in the brain, kidney, and bladder. In MKN45 cells, boron concentration increased in a time- and concentration-dependent manner. In both CDX and PDX animal models, the boron is preferentially distributed in tumor tissue rather than in blood or normal tissues. In addition, BPA had no significant adverse effects in rats. Taken together, the results suggested that BPA revealed a fast decrease in boron concentration in rats and is more likely to distribute in tumor cells and tissue., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tang, Wei, Zhang, Wang, Gu, Tang, Peng, Wei, Liu, Chen, Zhang, Gu and Li.)

Chimeric antigen receptor (CAR) -T cell therapy has become one of the hot topics in tumor immunity research in recent years. Although CAR-T cell therapy is highly effective in treating hematological malignancies, there are numerous obstacles that prevent CAR-T cells from having anti-tumor effects. Traditional CARs, from the first to the fourth generation, are incapable of completely overcoming these challenges. Therefore, identifying ways to boost the efficacy of CAR-T cells by utilizing the limited tumor surface antigens has become an urgent area of research. Certain special CARs that have special structures, special systems, or are greatly improved on the basis of traditional CARs, such as tandem CAR, dual-signaling CARs, AND-gate CARs, inhibitory CAR, AND-NOT CARs, CARs with three scFvs, ON/OFF-switch CARs, and universal CARs have been introduced. This study aims to use these special CARs to improve the anti-tumor ability, accuracy, and safety of CAR-T cells. In addition to summarizing various special CARs of T cells, this paper also expounds some of our own conjectures, aiming to provide reference and inspiration for CARs researchers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Miao, Zhang, Huang, Zhang, Wang, Tang, Teng and Li.)

Objectives: A bibliometric and knowledge-map analysis is used to explore hotspots' evolution and development trends in the CAR-T cell field. By looking for research hotspots and new topics, we can provide new clues and ideas for researchers in this field., Methods: The articles and reviews regarding CAR-T cells were retrieved and obtained from the Web of Science Core Collection (WOSCC) on October 28th, 2021. CtieSpace [version 5.8.R3 (64-bit)] and VOSviewer (version 1.6.17) were used to conduct the bibliometric and knowledge-map analysis., Results: 660 authors from 488 institutions in 104 countries/regions published 6,867 papers in 1,212 academic journals. The United States was absolutely in the leading position in this research field. The institution that contributed the most publications was the University of Pennsylvania. Carl H June published the most articles, while Shannon L Maude had the most co-citations. However, there was little cooperation between countries. After 2012, cooperation among various institutions was also small. The journals that published the most CAR-T cell-related papers were Frontiers in immunology and Cancers . Nevertheless, Blood and The New England Journal of Medicine were the most commonly co-cited journals. The most influential research hotspots were the research of CAR-T cells in hematological malignancies, the related research of cytokine release syndrome (CRS), CD19, and the anti-tumor activity and efficacy of CAR-T cells. The latest hotspots and topics included the study of CAR-T cells in solid tumors, universal CAR-T cells, CAR-NK cells, CD22, and anakinra (the IL-1 receptor antagonist). The research of CAR-T cells in solid tumors was a rapidly developing hot field. Emerging topics in this field mainly included the study of CAR-T cells in glioblastoma (related targets: IL13Rα2, EGFRvIII, and HER2), neuroblastoma (related target: GD2), sarcoma (related target: HER2), and pancreatic cancer (related target: mesothelin), especially glioblastoma., Conclusion: As an anti-tumor therapy with great potential and clinical application prospects, CAR-T cell therapy is still in a stage of rapid development. The related field of CAR-T cells will remain a research hotspot in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Miao, Zhang, Zhang, Wang, Tang, Teng and Li.)

T cell receptor-engineered T cell (TCR-T) therapy is free from the limit of surface antigen expression of the target cells, which is a potential cellular immunotherapy for cancer treatment. Significant advances in the treatment of hematologic malignancies with cellular immunotherapy have aroused the interest of researchers in the treatment of solid tumors. Nevertheless, the overall efficacy of TCR-T cell immunotherapy in solid tumors was not significantly high when compared with hematological malignancies. In this article, we pay attention to the barriers of TCR-T cell immunotherapy for solid tumors, as well as the strategies affecting the efficacy of TCR-T cell immunotherapy. To provide some reference for researchers to better overcome the impact of TCR-T cell efficiency in solid tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Yan, Zhang, Zhang, Tang, Han and Li.)

In recent years, chimeric antigen receptor T cells (CAR-T cells) have been faced with the problems of weak proliferation and poor persistence in the treatment of some malignancies. Researchers have been trying to perfect the function of CAR-T by genetically modifying its structure. In addition to the participation of T cell receptor (TCR) and costimulatory signals, immune cytokines also exert a decisive role in the activation and proliferation of T cells. Therefore, genetic engineering strategies were used to generate cytokines to enhance tumor killing function of CAR-T cells. When CAR-T cells are in contact with target tumor tissue, the proliferation ability and persistence of T cells can be improved by structurally or inductively releasing immunoregulatory molecules to the tumor region. There are a large number of CAR-T cells studies on gene-edited cytokines, and the most common cytokines involved are interleukins (IL-7, IL-12, IL-15, IL-18, IL-21, IL-23). Methods for the construction of gene-edited interleukin CAR-T cells include co-expression of single interleukin, two interleukin, interleukin combined with other cytokines, interleukin receptors, interleukin subunits, and fusion inverted cytokine receptors (ICR). Preclinical and clinical trials have yielded positive results, and many more are under way. By reading a large number of literatures, we summarized the functional characteristics of some members of the interleukin family related to tumor immunotherapy, and described the research status of gene-edited interleukin CAR-T cells in the treatment of malignant tumors. The objective is to explore the optimized strategy of gene edited interleukin-CAR-T cell function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Miao, Ren, Tang and Li.)

Chimeric antigen receptor (CAR) T-cell immunotherapy refers to an adoptive immunotherapy that has rapidly developed in recent years. It is a novel type of treatment that enables T cells to express specific CARs on their surface, then returns these T cells to tumor patients to kill the corresponding tumor cells. Significant strides in CAR-T cell immunotherapy against hematologic malignancies have elicited research interest among scholars in the treatment of solid tumors. Nonetheless, in contrast with the efficacy of CAR-T cell immunotherapy in the treatment of hematologic malignancies, its general efficacy against solid tumors is insignificant. This has been attributed to the complex biological characteristics of solid tumors. CAR-T cells play a better role in solid tumors, for instance by addressing obstacles including the lack of specific targets, inhibition of tumor microenvironment (TME), homing barriers of CAR-T cells, differentiation and depletion of CAR-T cells, inhibition of immune checkpoints, trogocytosis of CAR-T cells, tumor antigen heterogeneity, etc. This paper reviews the obstacles influencing the efficacy of CAR-T cell immunotherapy in solid tumors, their mechanism, and coping strategies, as well as economic restriction of CAR-T cell immunotherapy and its solutions. It aims to provide some references for researchers to better overcome the obstacles that affect the efficacy of CAR-T cells in solid tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Miao, Zhang, Ren, Tang and Li.)