A Pan-Histone Deacetylase Inhibitor Enhances the Antitumor Activity of B7-H3–Specific CAR T Cells in Solid Tumors

Lei, Xinyuan; Ou, Zhanpeng; Yang, Zhaohui; Zhong, Jianglong; Zhu, Ye; Tian, Jing; Wu, Jiarui; Deng, Heran; Lin, Xinyu; Peng, Yu; Li, Bowen; He, Lizhi; Tu, Zhiming; Chen, Weixiong; Li, Qunxing; Liu, Niu; Zhang, Hanqing; Wang, Zhangsong; Fang, Zezhen; Yamada, Teppei; Lv, Xiaobin; Tian, Tian; Pan, Guokai; Wu, Fan; Xiao, Liping; Zhang, Lizao; Cai, Tingting; Wang, Xinhui; Tannous, Bakhos A.; Li, Jinsong; Kontos, Filippos; Ferrone, Soldano; Fan, ST

doi:10.1158/1078-0432.ccr-20-2487

Cited by 34 publications

(19 citation statements)

References 53 publications

(68 reference statements)

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“…Recently, NK-cells have been used to generate CAR-NK cells, which controlled the growth of human NSCLC cells grafted in murine models and prolonged survival (95). Lei et al reported that a pan-histone deacetylase inhibitor can enhance the antitumor activity of B7-H3-specific CAR T cells in solid tumors (96).…”

Section: Targeting B7-h3 With Chimeric Antigen Receptor T Cells and Chimeric Antigen Receptor Nk Cellsmentioning

confidence: 99%

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B7-H3/CD276: An Emerging Cancer Immunotherapy

2021

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Immunotherapy aiming at suppressing tumor development by relying on modifying or strengthening the immune system prevails among cancer treatments and points out a new direction for cancer therapy. B7 homolog 3 protein (B7-H3, also known as CD276), a newly identified immunoregulatory protein member of the B7 family, is an attractive and promising target for cancer immunotherapy because it is overexpressed in tumor tissues while showing limited expression in normal tissues and participating in tumor microenvironment (TME) shaping and development. Thus far, numerous B7-H3-based immunotherapy strategies have demonstrated potent antitumor activity and acceptable safety profiles in preclinical models. Herein, we present the expression and biological function of B7-H3 in distinct cancer and normal cells, as well as B7-H3-mediated signal pathways in cancer cells and B7-H3-based tumor immunotherapy strategies. This review provides a comprehensive overview that encompasses B7-H3’s role in TME to its potential as a target in cancer immunotherapy.

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Section: Targeting B7-h3 With Chimeric Antigen Receptor T Cells and Chimeric Antigen Receptor Nk Cellsmentioning

confidence: 99%

“…Lei et al. reported that a pan-histone deacetylase inhibitor can enhance the antitumor activity of B7-H3-specific CAR T cells in solid tumors ( 96 ).…”

Section: B7-h3-based Tumor Immunotherapy Strategiesmentioning

confidence: 99%

B7-H3/CD276: An Emerging Cancer Immunotherapy

2021

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“…For instance, anti-HER2 CAR-T augmented with anti-PD-1 monoclonal antibody presented potent cytotoxicity, and thus regressed tumor growth in the trastuzumab-resistant breast cancer cell lines [ 191 ]. A deacetylase inhibitor SAHA administered with CAR-T recognizing B7-H3, an immune checkpoint, increased the expression of the target molecule at the transcriptional level and decreased the expression of CTLA-4 and TET2, a methylcytosine hydroxylating enzyme, on effector cells [ 192 ].…”

Section: Strategies To Overcome Immunotherapy Resistance Of Breast Cancermentioning

confidence: 99%

The Immune Landscape of Breast Cancer: Strategies for Overcoming Immunotherapy Resistance

Retecki

Seweryn

Graczyk-Jarzynka

et al. 2021

Cancers

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Breast cancer (BC) has traditionally been considered to be not inherently immunogenic and insufficiently represented by immune cell infiltrates. Therefore, for a long time, it was thought that the immunotherapies targeting this type of cancer and its microenvironment were not justified and would not bring benefits for breast cancer patients. Nevertheless, to date, a considerable number of reports have indicated tumor-infiltrating lymphocytes (TILs) as a prognostic and clinically relevant biomarker in breast cancer. A high TILs expression has been demonstrated in primary tumors, of both, HER2-positive BC and triple-negative (TNBC), of patients before treatment, as well as after treatment with adjuvant and neoadjuvant chemotherapy. Another milestone was reached in advanced TNBC immunotherapy with the help of the immune checkpoint inhibitors directed against the PD-L1 molecule. Although those findings, together with the recent developments in chimeric antigen receptor T cell therapies, show immense promise for significant advancements in breast cancer treatments, there are still various obstacles to the optimal activity of immunotherapeutics in BC treatment. Of these, the immunosuppressive tumor microenvironment constitutes a key barrier that greatly hinders the success of immunotherapies in the most aggressive types of breast cancer, HER2-positive and TNBC. Therefore, the improvement of the current and the demand for the development of new immunotherapeutic strategies is strongly warranted.

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“…Of note, our results have distinguished that B7-H3, also known as CD276, might be a promising therapeutic target for CAR-based therapy, and there is evidence that it carries no risk of on-target off-tumor toxicity ( 57 , 58 ). Recently, our research team also found that SAHA, a pan histone deacetylase inhibitor, could enhance B7-H3.CAR-T cells in solid tumors ( 59 ). Elsewhere, novel approaches have been investigated to overcome biological barriers in solid tumors, for example, using local delivery systems; applying anti-vasculature agents, chemokines or oncolytic viruses; and equipping effector immune cells with the ability to generate chemokines or heparinase to degrade the extracellular matrix ( 60 ).…”

Section: Discussionmentioning

confidence: 98%

Bibliometric Analysis of Chimeric Antigen Receptor-Based Immunotherapy in Cancers From 2001 to 2021

Qiu

Rong

et al. 2022

Front. Immunol.

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BackgroundChimeric antigen receptor (CAR)-based immunotherapy has shown great potential for the treatment of both hematopoietic malignancies and solid tumors. Nevertheless, multiple obstacles still block the development of CAR-based immunotherapy in the clinical setting. In this study, we aimed to summarize the research landscape and highlight the front lines and trends of this field.MethodsLiterature published from 2001 to 2021 was searched in the Web of Science Core Collection database. Full records and cited references of all the documents were extracted and screened. Bibliometric analysis and visualization were conducted using CiteSpace, Microsoft Excel 2019, VOSviewer and R software.ResultsA total of 5981 articles and reviews were included. The publication and citation results exhibited increasing trends in the last 20 years. Frontiers in Immunology and Blood were the most productive and most co-cited journals, respectively. The United States was the country with the most productive organizations and publications in the comprehensive worldwide cooperation network, followed by China and Germany. June, C.H. published the most papers with the most citations, while Maude, S.L. ranked first among the co-cited authors. The hotspots in CAR-based therapy research were multiple myeloma, safety and toxicity, solid tumors, CAR-engineered immune cells beyond T cells, and gene editing.ConclusionCAR-based immunotherapy is a promising treatment for cancer patients, and there is an emerging movement toward using advanced gene modification technologies to overcome therapeutic challenges, especially in solid tumors, and to generate safer and more effective universal CAR-engineered cell products.

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A Pan-Histone Deacetylase Inhibitor Enhances the Antitumor Activity of B7-H3–Specific CAR T Cells in Solid Tumors

Cited by 34 publications

References 53 publications

B7-H3/CD276: An Emerging Cancer Immunotherapy

B7-H3/CD276: An Emerging Cancer Immunotherapy

The Immune Landscape of Breast Cancer: Strategies for Overcoming Immunotherapy Resistance

Bibliometric Analysis of Chimeric Antigen Receptor-Based Immunotherapy in Cancers From 2001 to 2021

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