Cancer gene therapy最新文献_第10页

Phosphoglycerate mutase 1 promotes breast cancer progression through inducing immunosuppressive M2 macrophages 磷酸甘油酸突变酶 1 通过诱导免疫抑制性 M2 巨噬细胞促进乳腺癌的进展。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-05-15 DOI: 10.1038/s41417-024-00769-5

Dong Zhang, Min Wang, Shiya Ma, Min Liu, Wenwen Yu, Xiying Zhang, Ting Liu, Shaochuan Liu, Xiubao Ren, Qian Sun

{"title":"Phosphoglycerate mutase 1 promotes breast cancer progression through inducing immunosuppressive M2 macrophages","authors":"Dong Zhang, Min Wang, Shiya Ma, Min Liu, Wenwen Yu, Xiying Zhang, Ting Liu, Shaochuan Liu, Xiubao Ren, Qian Sun","doi":"10.1038/s41417-024-00769-5","DOIUrl":"10.1038/s41417-024-00769-5","url":null,"abstract":"Immunosuppressive tumor microenvironment (TME) contributes to tumor progression and causes major obstacles for cancer therapy. Phosphoglycerate mutase 1 (PGAM1) is a key enzyme involved in cancer metabolism while its role in remodeling TME remains unclear. In this study, we reported that PGAM1 suppression in breast cancer (BC) cells led to a decrease in M2 polarization, migration, and interleukin-10 (IL-10) production of macrophages. PGAM1 regulation on CCL2 expression was essential to macrophage recruitment, which further mediated by activating JAK-STAT pathway. Additionally, the CCL2/CCR2 axis was observed to participate in PGAM1-mediated immunosuppression via regulating PD-1 expression in macrophages. Combined targeting of PGAM1 and the CCL2/CCR2 axis led to a reduction in tumor growth in vivo. Furthermore, clinical validation in BC tissues indicated a positive correlation between PGAM1, CCL2 and macrophage infiltration. Our study provides novel insights into the induction of immunosuppressive TME by PGAM1 and propose a new strategy for combination therapies targeting PGAM1 and macrophages in BC.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 7","pages":"1018-1033"},"PeriodicalIF":4.8,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dickkopf-1 (DKK1) drives growth and metastases in castration-resistant prostate cancer Dickkopf-1（DKK1）能促进耐受性前列腺癌的生长和转移。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-05-13 DOI: 10.1038/s41417-024-00783-7

Letizia Rinella, Gloria Fiorentino, Mara Compagno, Cristina Grange, Massimo Cedrino, Francesca Marano, Ornella Bosco, Elena Vissio, Luisa Delsedime, Patrizia D’Amelio, Benedetta Bussolati, Emanuela Arvat, Maria Graziella Catalano

{"title":"Dickkopf-1 (DKK1) drives growth and metastases in castration-resistant prostate cancer","authors":"Letizia Rinella, Gloria Fiorentino, Mara Compagno, Cristina Grange, Massimo Cedrino, Francesca Marano, Ornella Bosco, Elena Vissio, Luisa Delsedime, Patrizia D’Amelio, Benedetta Bussolati, Emanuela Arvat, Maria Graziella Catalano","doi":"10.1038/s41417-024-00783-7","DOIUrl":"10.1038/s41417-024-00783-7","url":null,"abstract":"Metastatic castration-resistant prostate cancer (mCRPC) is associated with a poor prognosis and remains an incurable fatal disease. Therefore, the identification of molecular markers involved in cancer progression is urgently needed to develop more-effective therapies. The present study investigated the role of the Wnt signaling modulator Dickkopf-1 (DKK1) in the growth and metastatic progression of mCRPC. DKK1 silencing through siRNA and deletion via CRISPR/Cas9 editing were performed in two different metastatic castration-resistant prostate cancer cell lines (PC3 and DU145). A xenograft tumor model was used to assess tumor growth and metastases. In in vitro experiments, both DKK1 silencing and deletion reduced cell growth and migration of both cell lines. DKK1 knockout clones (DKK1-KO) exhibited cell cycle arrest, tubulin reorganization, and modulation of tumor metastasis-associated genes. Furthermore, in DKK1-KO cells, E-cadherin re-expression and its membrane co-localization with β-catenin were observed, contributing to reduced migration; Cadherin-11, known to increase during epithelial-mesenchymal transition, was down-regulated in DKK1-KO cells. In the xenograft mouse model, DKK1 deletion not only reduced tumor growth but also inhibited the formation of lung metastases. In conclusion, our findings support the key role of DKK1 in the growth and metastatic dissemination of mCRPC, both in vitro and in vivo.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 8","pages":"1266-1279"},"PeriodicalIF":4.8,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting KRASG12D mutation in non-small cell lung cancer: molecular mechanisms and therapeutic potential 针对非小细胞肺癌中的 KRASG12D 突变：分子机制和治疗潜力。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-05-11 DOI: 10.1038/s41417-024-00778-4

Yining Tang, Xi Pu, Xiao Yuan, Zhonghao Pang, Feng Li, Xu Wang

{"title":"Targeting KRASG12D mutation in non-small cell lung cancer: molecular mechanisms and therapeutic potential","authors":"Yining Tang, Xi Pu, Xiao Yuan, Zhonghao Pang, Feng Li, Xu Wang","doi":"10.1038/s41417-024-00778-4","DOIUrl":"10.1038/s41417-024-00778-4","url":null,"abstract":"Lung malignant tumors are a type of cancer with high incidence and mortality rates worldwide. Non-small cell lung cancer (NSCLC) accounts for over 80% of all lung malignant tumors, and most patients are diagnosed at advanced stages, leading to poor prognosis. Over the past decades, various oncogenic driver alterations associated with lung cancer have been identified, each of which can potentially serve as a therapeutic target. Rat sarcoma (RAS) genes are the most commonly mutated oncogenes in human cancers, with Kirsten rat sarcoma (KRAS) being the most common subtype. The role of KRAS oncogene in NSCLC is still not fully understood, and its impact on prognosis remains controversial. Despite the significant advancements in targeted therapy and immune checkpoint inhibitors (ICI) that have transformed the treatment landscape of advanced NSCLC in recent years, targeting KRAS (both directly and indirectly) remains challenging and is still under intensive research. In recent years, significant progress has been made in the development of targeted drugs targeting the NSCLC KRASG12C mutant subtype. However, research progress on target drugs for the more common KRASG12D subtype has been slow, and currently, no specific drugs have been approved for clinical use, and many questions remain to be answered, such as the mechanisms of resistance in this subtype of NSCLC, how to better utilize combination strategies with multiple treatment modalities, and whether KRASG12D inhibitors offer substantial efficacy in the treatment of advanced NSCLC patients.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 7","pages":"961-969"},"PeriodicalIF":4.8,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00778-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TRIM58 downregulation maintains stemness via MYH9-GRK3-YAP axis activation in triple-negative breast cancer stem cells TRIM58 下调可通过激活三阴性乳腺癌干细胞中的 MYH9-GRK3-YAP 轴维持干性。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-05-07 DOI: 10.1038/s41417-024-00780-w

Xujun Li, Jing Jiang, Qian Wu, Tianzi You, Fan Yang

{"title":"TRIM58 downregulation maintains stemness via MYH9-GRK3-YAP axis activation in triple-negative breast cancer stem cells","authors":"Xujun Li, Jing Jiang, Qian Wu, Tianzi You, Fan Yang","doi":"10.1038/s41417-024-00780-w","DOIUrl":"10.1038/s41417-024-00780-w","url":null,"abstract":"TRIM58 is a member of the TRIM protein family, which possess with E3 ubiquitin ligase activities. Studies have revealed that low expression of TRIM58 plays key roles, has been implicated in the tumor progression of tumor formation due to its reduced expression. However, its role in regulating the stemness of breast cancer stem cells (CSCs) remains unexplored. Here, we found that TRIM58 was underexpressed in TNBC tissues and cells compared to adjacent mucosa tissue, and its downregulation was significantly associated with shorter survival. Overexpression of TRIM58 reduced the proportion of CD44 + /CD24- cells, upregulated differentiation genes, and inhibited stemness-related gene expression in TNBC CSCs. In vitro and in vivo experiments revealed that TRIM58 overexpression in CSCs suppressed tumor sphere formation and tumorigenic capacity. Co-IP results indicated direct interaction between TRIM58 and MYH9, with TRIM58 inducing MYH9 degradation via ubiquitination in differentiated cells. Label-free quantitative proteomics identified GRK3 and Hippo-YAP as downstream targets and signaling pathways of MYH9. TIMER database analysis, immunohistochemistry, western blotting, DNA-protein pulldown experiments, and dual luciferase reporter assays demonstrated that MYH9 regulated GRK3 transcriptional activation in CSCs. In conclusion, elevated TRIM58 expression in CSCs downregulates MYH9 protein levels by promoting ubiquitin-mediated degradation, thereby inhibiting downstream GRK3 transcription, inactivating the YAP stemness pathway, and ultimately promoting CSC differentiation.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 8","pages":"1186-1200"},"PeriodicalIF":4.8,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Editorial Expression of Concern: Herpes simplex virus thymidine kinase/ganciclovir–induced cell death is enhanced by co-expression of caspase-3 in ovarian carcinoma cells 社论表达的关切：卵巢癌细胞中，单纯疱疹病毒胸苷激酶/更昔洛韦诱导的细胞死亡因同时表达 Caspase-3 而增强。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-05-02 DOI: 10.1038/s41417-024-00777-5

I. A. McNeish, T. Tenev, S. Bell, M. Marani, G. Vassaux, N. Lemoine

引用次数: 0

Mesenchymal stem cells as therapeutic vehicles for glioma 间充质干细胞作为胶质瘤的治疗工具。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-04-23 DOI: 10.1038/s41417-024-00775-7

Tomoya Oishi, Shinichiro Koizumi, Kazuhiko Kurozumi

{"title":"Mesenchymal stem cells as therapeutic vehicles for glioma","authors":"Tomoya Oishi, Shinichiro Koizumi, Kazuhiko Kurozumi","doi":"10.1038/s41417-024-00775-7","DOIUrl":"10.1038/s41417-024-00775-7","url":null,"abstract":"Glioma is a disease with a poor prognosis despite the availability of multimodality treatments, and the development of novel therapies is urgently needed. Challenges in glioma treatment include the difficulty for drugs to cross the blood–brain barrier when administered systemically and poor drug diffusion when administered locally. Mesenchymal stem cells exhibit advantages for glioma therapy because of their ability to pass through the blood–brain barrier and migrate to tumor cells and their tolerance to the immune system. Therefore, mesenchymal stem cells have been explored as vehicles for various therapeutic agents for glioma treatment. Mesenchymal stem cells loaded with chemotherapeutic drugs show improved penetration and tumor accumulation. For gene therapy, mesenchymal stem cells can be used as vehicles for suicide genes, the so-called gene-directed enzyme prodrug therapy. Mesenchymal stem cell-based oncolytic viral therapies have been attempted in recent years to enhance the efficacy of infection against the tumor, viral replication, and distribution of viral particles. Many uncertainties remain regarding the function and behavior of mesenchymal stem cells in gliomas. However, strategies to increase mesenchymal stem cell migration to gliomas may improve the delivery of therapeutic agents and enhance their anti-tumor effects, representing promising potential for patient treatment.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 9","pages":"1306-1314"},"PeriodicalIF":4.8,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00775-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140669467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

miR-451a was selectively sorted into exosomes and promoted the progression of esophageal squamous cell carcinoma through CAB39 miR-451a 被选择性地分类到外泌体中，并通过 CAB39 促进食管鳞状细胞癌的进展

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-04-22 DOI: 10.1038/s41417-024-00774-8

Lu Wang, Huijuan Liu, Qinglu Wu, Yiqian Liu, Zhenpeng Yan, Guohui Chen, Yao Shang, Songrui Xu, Qichao Zhou, Ting Yan, Xiaolong Cheng

{"title":"miR-451a was selectively sorted into exosomes and promoted the progression of esophageal squamous cell carcinoma through CAB39","authors":"Lu Wang, Huijuan Liu, Qinglu Wu, Yiqian Liu, Zhenpeng Yan, Guohui Chen, Yao Shang, Songrui Xu, Qichao Zhou, Ting Yan, Xiaolong Cheng","doi":"10.1038/s41417-024-00774-8","DOIUrl":"10.1038/s41417-024-00774-8","url":null,"abstract":"Exosomes are emerging mediators of cell-cell communication, which are secreted from cells and may be delivered into recipient cells in cell biological processes. Here, we examined microRNA (miRNA) expression in esophageal squamous cell carcinoma (ESCC) cells. We performed miRNA sequencing in exosomes and cells of KYSE150 and KYSE450 cell lines. Among these differentially expressed miRNAs, 20 of the miRNAs were detected in cells and exosomes. A heat map indicated that the level of miR-451a was higher in exosomes than in ESCC cells. Furthermore, miRNA pull-down assays and combined exosomes proteomic data showed that miR-451a interacts with YWHAE. Over-expression of YWHAE leads to miR-451a accumulation in the exosomes instead of the donor cells. We found that miR-451a was sorted into exosomes. However, the biological function of miR-451a remains unclear in ESCC. Here, Dual-luciferase reporter assay was conducted and it was proved that CAB39 is a target gene of miR-451a. Moreover, CAB39 is related to TGF-β1 from RNA-sequencing data of 155 paired of ESCC tissues and the matched tissues. Western Blot and qPCR revealed that CAB39 and TGF-β1 were positively correlated in ESCC. Over-expression of CAB39 were cocultured with PBMCs from the blood from healthy donors. Flow cytometry assays showed that apoptotic cells were significantly reduced after CAB39 over-expression and significantly increased after treated with TGF-β1 inhibitors. Thus, our data indicate that CAB39 weakens antitumor immunity through TGF-β1 in ESCC. In summary, YWHAE selectively sorted miR-451a into exosomes and it can weaken antitumor immunity promotes tumor progression through CAB39.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 7","pages":"1060-1069"},"PeriodicalIF":4.8,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140635102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cleavage and polyadenylation machinery as a novel targetable vulnerability for human cancer 裂解和多聚腺苷酸化机制是人类癌症的新型靶向漏洞

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-04-17 DOI: 10.1038/s41417-024-00770-y

Giulia Pagani, Paolo Gandellini

{"title":"Cleavage and polyadenylation machinery as a novel targetable vulnerability for human cancer","authors":"Giulia Pagani, Paolo Gandellini","doi":"10.1038/s41417-024-00770-y","DOIUrl":"10.1038/s41417-024-00770-y","url":null,"abstract":"The role of alternative polyadenylation of mRNA in sustaining aggressive features of tumors is quite well established, as it is responsible for the 3’UTR shortening of oncogenes and subsequent relief from miRNA-mediated repression observed in cancer cells. However, the information regarding the vulnerability of cancer cells to the inhibition of cleavage and polyadenylation (CPA) machinery is very scattered. Only few recent reports show the antitumor activity of pharmacological inhibitors of CPSF3, one among CPA factors. More in general, the fact that deregulated CPA can be seen as a new hallmark of cancer and as a potential reservoir of novel therapeutic targets has never been formalized. Here, to extend our view on the potential of CPA inhibition (CPAi) approaches as anticancer therapies, we systematically tested the fitness of about one thousand cell lines of different cancer types upon depletion of all known CPA factors by interrogating genome-scale CRISPR and RNAi dependency maps of the DepMap project. Our analysis confirmed core and accessory CPA factors as novel vulnerabilities for human cancer, thus highlighting the potential of CPAi as anticancer therapy. Among all, CPSF1 appeared as a promising actionable candidate for drug development, as it showed low dependency scores pancancer and particularly in highly proliferating cells. In a personalized medicine perspective, the observed differential vulnerability of cancer cell lines to selected CPA factors may be used to build up signatures to predict response of individual human tumors to CPAi approaches.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 7","pages":"957-960"},"PeriodicalIF":4.8,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140608661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of the galactosyltransferase C1GALT1 reduces osteosarcoma cell proliferation by interfering with ERK signaling and cell cycle progression 抑制半乳糖基转移酶 C1GALT1 可通过干扰 ERK 信号传导和细胞周期进展减少骨肉瘤细胞增殖

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-04-15 DOI: 10.1038/s41417-024-00773-9

Kentaro Watanabe, Keiji Tasaka, Hideto Ogata, Shota Kato, Hiroo Ueno, Katsutsugu Umeda, Tomoya Isobe, Yasuo Kubota, Masahiro Sekiguchi, Shunsuke Kimura, Aiko Sato-Otsubo, Mitsuteru Hiwatari, Tetsuo Ushiku, Motohiro Kato, Akira Oka, Satoru Miyano, Seishi Ogawa, Junko Takita

{"title":"Inhibition of the galactosyltransferase C1GALT1 reduces osteosarcoma cell proliferation by interfering with ERK signaling and cell cycle progression","authors":"Kentaro Watanabe, Keiji Tasaka, Hideto Ogata, Shota Kato, Hiroo Ueno, Katsutsugu Umeda, Tomoya Isobe, Yasuo Kubota, Masahiro Sekiguchi, Shunsuke Kimura, Aiko Sato-Otsubo, Mitsuteru Hiwatari, Tetsuo Ushiku, Motohiro Kato, Akira Oka, Satoru Miyano, Seishi Ogawa, Junko Takita","doi":"10.1038/s41417-024-00773-9","DOIUrl":"10.1038/s41417-024-00773-9","url":null,"abstract":"Novel therapeutic strategies are urgently required for osteosarcoma, given the early age at onset and persistently high mortality rate. Modern transcriptomics techniques can identify differentially expressed genes (DEGs) that may serve as biomarkers and therapeutic targets, so we screened for DEGs in osteosarcoma. We found that osteosarcoma cases could be divided into fair and poor survival groups based on gene expression profiles. Among the genes upregulated in the poor survival group, siRNA-mediated knockdown of the glycosylation-related gene C1GALT1 suppressed osteosarcoma cell proliferation in culture. Gene expression, phosphorylation, and glycome array analyses also demonstrated that C1GALT1 is required to maintain ERK signaling and cell cycle progression. Moreover, the C1GALT1 inhibitor itraconazole suppressed osteosarcoma cell proliferation in culture, while doxycycline-induced shRNA-mediated knockdown reduced xenograft osteosarcoma growth in mice. Elevated C1GALT1 expression is a potential early predictor of poor prognosis, while pharmacological inhibition may be a feasible treatment strategy for osteosarcoma.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 7","pages":"1049-1059"},"PeriodicalIF":4.8,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00773-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140585839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CRISPR-Cas gene knockouts to optimize engineered T cells for cancer immunotherapy 利用 CRISPR-Cas 基因敲除技术优化用于癌症免疫疗法的工程 T 细胞

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-04-12 DOI: 10.1038/s41417-024-00771-x

Valentine De Castro, Jeanne Galaine, Romain Loyon, Yann Godet

{"title":"CRISPR-Cas gene knockouts to optimize engineered T cells for cancer immunotherapy","authors":"Valentine De Castro, Jeanne Galaine, Romain Loyon, Yann Godet","doi":"10.1038/s41417-024-00771-x","DOIUrl":"10.1038/s41417-024-00771-x","url":null,"abstract":"While CAR-T and tgTCR-T therapies have exhibited noteworthy and promising outcomes in hematologic and solid tumors respectively, a set of distinct challenges remains. Consequently, the quest for novel strategies has become imperative to safeguard and more effectively release the full functions of engineered T cells. These factors are intricately linked to the success of adoptive cell therapy. Recently, CRISPR-based technologies have emerged as a major breakthrough for maintaining T cell functions. These technologies have allowed the discovery of T cells’ negative regulators such as specific cell-surface receptors, cell-signaling proteins, and transcription factors that are involved in the development or maintenance of T cell dysfunction. By employing a CRISPR-genic invalidation approach to target these negative regulators, it has become possible to prevent the emergence of hypofunctional T cells. This review revisits the establishment of the dysfunctional profile of T cells before delving into a comprehensive summary of recent CRISPR-gene invalidations, with each invalidation contributing to the enhancement of engineered T cells’ antitumor capacities. The narrative unfolds as we explore how these advancements were discovered and identified, marking a significant advancement in the pursuit of superior adoptive cell therapy.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 8","pages":"1124-1134"},"PeriodicalIF":4.8,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00771-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140585743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0