Cancer gene therapy最新文献_第9页

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

Correction: SPRTN is involved in hepatocellular carcinoma development through the ER stress response 更正：SPRTN 通过 ER 应激反应参与肝细胞癌的发展。

IF 6.4 3区医学

Cancer gene therapy Pub Date : 2024-04-10 DOI: 10.1038/s41417-024-00772-w

Anja Batel, Mirjana Polović, Mateo Glumac, Oliver Šuman, Stipislav Jadrijević, Bernarda Lozić, Marija Petrović, Bobana Samardžija, Nicholas J. Bradshaw, Karlo Skube, Vinko Palada, Mislav Acman, Ivana Marinović Terzić

引用次数: 0

Understanding, diagnosing, and treating pancreatic cancer from the perspective of telomeres and telomerase 从端粒和端粒酶的角度了解、诊断和治疗胰腺癌

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-04-09 DOI: 10.1038/s41417-024-00768-6

Songting Shou, Yuanliang Li, Jiaqin Chen, Xing Zhang, Chuanlong Zhang, Xiaochen Jiang, Fudong Liu, Li Yi, Xiyuan Zhang, En Geer, Zhenqing Pu, Bo Pang

{"title":"Understanding, diagnosing, and treating pancreatic cancer from the perspective of telomeres and telomerase","authors":"Songting Shou, Yuanliang Li, Jiaqin Chen, Xing Zhang, Chuanlong Zhang, Xiaochen Jiang, Fudong Liu, Li Yi, Xiyuan Zhang, En Geer, Zhenqing Pu, Bo Pang","doi":"10.1038/s41417-024-00768-6","DOIUrl":"10.1038/s41417-024-00768-6","url":null,"abstract":"Telomerase is associated with cellular aging, and its presence limits cellular lifespan. Telomerase by preventing telomere shortening can extend the number of cell divisions for cancer cells. In adult pancreatic cells, telomeres gradually shorten, while in precancerous lesions of cancer, telomeres in cells are usually significantly shortened. At this time, telomerase is still in an inactive state, and it is not until before and after the onset of cancer that telomerase is reactivated, causing cancer cells to proliferate. Methylation of the telomerase reverse transcriptase (TERT) promoter and regulation of telomerase by lactate dehydrogenase B (LDHB) is the mechanism of telomerase reactivation in pancreatic cancer. Understanding the role of telomeres and telomerase in pancreatic cancer will help to diagnose and initiate targeted therapy as early as possible. This article reviews the role of telomeres and telomerase as biomarkers in the development of pancreatic cancer and the progress of research on telomeres and telomerase as targets for therapeutic intervention.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 9","pages":"1292-1305"},"PeriodicalIF":4.8,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00768-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140585895","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

RevCAR-expressing immune effector cells for targeting of Fn14-positive glioblastoma 表达 RevCAR 的免疫效应细胞用于靶向治疗 Fn14 阳性胶质母细胞瘤

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-04-06 DOI: 10.1038/s41417-024-00766-8

Haidy A. Saleh, Nicola Mitwasi, Liliana R. Loureiro, Alexandra Kegler, Karla Elizabeth González Soto, Lydia Hoffmann, Eugenia Crespo, Claudia Arndt, Ralf Bergmann, Michael Bachmann, Anja Feldmann

{"title":"RevCAR-expressing immune effector cells for targeting of Fn14-positive glioblastoma","authors":"Haidy A. Saleh, Nicola Mitwasi, Liliana R. Loureiro, Alexandra Kegler, Karla Elizabeth González Soto, Lydia Hoffmann, Eugenia Crespo, Claudia Arndt, Ralf Bergmann, Michael Bachmann, Anja Feldmann","doi":"10.1038/s41417-024-00766-8","DOIUrl":"10.1038/s41417-024-00766-8","url":null,"abstract":"In recent studies, we have established the unique adapter chimeric antigen receptor (CAR) platform RevCAR which uses, as an extracellular CAR domain, a peptide epitope instead of an antibody domain. RevCAR adapters (termed RevCAR target modules, RevTMs) are bispecific antibodies that enable the reversible ON/OFF switch of the RevCAR system, improving the safety compared to conventional CARs. Here, we describe for the first time its use for retargeting of both T and NK-92 cells. In addition, we describe the development and preclinical validation of a novel RevTM for targeting of the fibroblast growth factor-inducible 14 (Fn14) surface receptor which is overexpressed on Glioblastoma (GBM) cells, and therefore serves as a promising target for the treatment of GBM. The novel RevTM efficiently redirects RevCAR modified T and NK-92 cells and leads to the killing of GBM cells both in vitro and in vivo. Tumor cell killing is associated with increased IL-2, TNF-α and/or IFN-γ secretion. Hence, these findings give an insight into the complementary potential of both RevCAR T and NK-92 systems as a safe and specific immunotherapeutic approach against GBM.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 9","pages":"1323-1334"},"PeriodicalIF":4.8,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00766-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586221","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

SDCBP modulates tumor microenvironment, tumor progression and anti-PD1 efficacy in colorectal cancer SDCBP 可调节结直肠癌的肿瘤微环境、肿瘤进展和抗 PD1 的疗效。

IF 6.4 3区医学

Cancer gene therapy Pub Date : 2024-03-30 DOI: 10.1038/s41417-024-00758-8

Jiahua Yu, Shijun Yu, Jin Bai, Zhe Zhu, Yong Gao, Yandong Li

{"title":"SDCBP modulates tumor microenvironment, tumor progression and anti-PD1 efficacy in colorectal cancer","authors":"Jiahua Yu, Shijun Yu, Jin Bai, Zhe Zhu, Yong Gao, Yandong Li","doi":"10.1038/s41417-024-00758-8","DOIUrl":"10.1038/s41417-024-00758-8","url":null,"abstract":"Anti-programmed cell death 1 (aPD1) therapy has yielded limited success in patients with colorectal cancer (CRC). Syndecan binding protein (SDCBP), encodes a PDZ domain-containing protein that is essential for cellular processes, including cell adhesion, migration, and signal transduction. Here, we investigated the effect of SDCBP on tumor progression, immunotherapy, and the tumor microenvironment (TME) in CRC. High expression of SDCBP is associated with non-response to immunotherapy and correlated with poorer disease-free survival (DFS) in CRC patients. Inhibiting SDCBP by transfecting shRNA or using its inhibitor zinc pyrithione (ZnPT) hindered proliferation and metastasis while enhancing the efficacy of aPD1 treatment in a mouse xenograft model and liver metastasis model. The TME of CRC was significantly altered following ZnPT treatment characterized by a reduced amount of M2 macrophages and a heightened percentage of M1 macrophages. The co-culture system of CRC cells and macrophages provided evidence that SDCBP silencing promoted the repolarisation of M2 macrophages into M1. SDCBP promotes the proliferation, metastasis, and immunotherapy resistance of CRC. Thus, ZnPT represents an effective SDCBP inhibitor and exhibits considerable potential for combination with aPD1 to enhance immunotherapy efficacy.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 5","pages":"755-765"},"PeriodicalIF":6.4,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329650","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

PANoptosis: bridging apoptosis, pyroptosis, and necroptosis in cancer progression and treatment PANoptosis：在癌症进展和治疗中连接凋亡、热凋亡和坏死。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-03-29 DOI: 10.1038/s41417-024-00765-9

Jie Gao, Anying Xiong, Jiliu Liu, Xiaolan Li, Junyi Wang, Lei Zhang, Yao Liu, Ying Xiong, Guoping Li, Xiang He

{"title":"PANoptosis: bridging apoptosis, pyroptosis, and necroptosis in cancer progression and treatment","authors":"Jie Gao, Anying Xiong, Jiliu Liu, Xiaolan Li, Junyi Wang, Lei Zhang, Yao Liu, Ying Xiong, Guoping Li, Xiang He","doi":"10.1038/s41417-024-00765-9","DOIUrl":"10.1038/s41417-024-00765-9","url":null,"abstract":"This comprehensive review explores the intricate mechanisms of PANoptosis and its implications in cancer. PANoptosis, a convergence of apoptosis, pyroptosis, and necroptosis, plays a crucial role in cell death and immune response regulation. The study delves into the molecular pathways of each cell death mechanism and their crosstalk within PANoptosis, emphasizing the shared components like caspases and the PANoptosome complex. It highlights the significant role of PANoptosis in various cancers, including respiratory, digestive, genitourinary, gliomas, and breast cancers, showing its impact on tumorigenesis and patient survival rates. We further discuss the interwoven relationship between PANoptosis and the tumor microenvironment (TME), illustrating how PANoptosis influences immune cell behavior and tumor progression. It underscores the dynamic interplay between tumors and their microenvironments, focusing on the roles of different immune cells and their interactions with cancer cells. Moreover, the review presents new breakthroughs in cancer therapy, emphasizing the potential of targeting PANoptosis to enhance anti-tumor immunity. It outlines various strategies to manipulate PANoptosis pathways for therapeutic purposes, such as targeting key signaling molecules like caspases, NLRP3, RIPK1, and RIPK3. The potential of novel treatments like immunogenic PANoptosis-initiated therapies and nanoparticle-based strategies is also explored.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 7","pages":"970-983"},"PeriodicalIF":4.8,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00765-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140326369","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

Generation of glioblastoma in mice engrafted with human cytomegalovirus-infected astrocytes 巨细胞病毒感染星形胶质细胞接种小鼠后产生胶质母细胞瘤。

IF 4.8 3区医学

Cancer gene therapy Pub Date : 2024-03-29 DOI: 10.1038/s41417-024-00767-7

Joris Guyon, Sandy Haidar Ahmad, Ranim El Baba, Mégane Le Quang, Andreas Bikfalvi, Thomas Daubon, Georges Herbein

{"title":"Generation of glioblastoma in mice engrafted with human cytomegalovirus-infected astrocytes","authors":"Joris Guyon, Sandy Haidar Ahmad, Ranim El Baba, Mégane Le Quang, Andreas Bikfalvi, Thomas Daubon, Georges Herbein","doi":"10.1038/s41417-024-00767-7","DOIUrl":"10.1038/s41417-024-00767-7","url":null,"abstract":"Mounting evidence is identifying human cytomegalovirus (HCMV) as a potential oncogenic virus. HCMV has been detected in glioblastoma multiforme (GB). Herewith, we present the first experimental evidence for the generation of CMV-Elicited Glioblastoma Cells (CEGBCs) possessing glioblastoma-like traits that lead to the formation of glioblastoma in orthotopically xenografted mice. In addition to the already reported oncogenic HCMV-DB strain, we isolated three HCMV clinical strains from GB tissues that transformed HAs toward CEGBCs and generated spheroids from CEGBCs that resulted in the appearance of glioblastoma-like tumors in xenografted mice. These tumors were nestin-positive mostly in the invasive part surrounded by GFAP-positive reactive astrocytes. The glioblastoma immunohistochemistry phenotype was confirmed by EGFR and cMet gene amplification in the tumor parallel to the detection of HCMV IE and UL69 genes and proteins. Our results fit with an HCMV-induced glioblastoma model of oncogenesis in vivo which will open the door to new therapeutic approaches and assess the anti-HCMV treatment as well as immunotherapy in fighting GB which is characterized by poor prognosis.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 7","pages":"1070-1080"},"PeriodicalIF":4.8,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41417-024-00767-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140326368","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

Gastrointestinal infections and gastrointestinal haemorrhage are underestimated but serious adverse events in chimeric antigen receptor T-cell recipients: A real-world study 在嵌合抗原受体 T 细胞受者中，胃肠道感染和胃肠道出血是被低估的严重不良事件：真实世界研究

IF 6.4 3区医学

Cancer gene therapy Pub Date : 2024-03-28 DOI: 10.1038/s41417-024-00752-0

Zhiqiang Song, Yang Wang, Ping Liu, Yuke Geng, Na Liu, Jie Chen, Jianmin Yang

{"title":"Gastrointestinal infections and gastrointestinal haemorrhage are underestimated but serious adverse events in chimeric antigen receptor T-cell recipients: A real-world study","authors":"Zhiqiang Song, Yang Wang, Ping Liu, Yuke Geng, Na Liu, Jie Chen, Jianmin Yang","doi":"10.1038/s41417-024-00752-0","DOIUrl":"10.1038/s41417-024-00752-0","url":null,"abstract":"Chimeric antigen receptor T-cell (CAR-T) therapy has achieved durable response in patients with hematological malignancies, however, therapy-associated multisystem toxicities are commonly observed. Here, we systematically analyzed CAR-T-related gastrointestinal adverse events (GAEs) using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) between January 2017 and December 2021. Disproportionality analyses were performed using reporting odds ratios (ROR) and information component (IC). Among 105,087,611 reports in FAERS, 1518 CAR-T-related GAEs reports were identified. 23 GAEs (n = 281, 18.51%) were significantly overreported following CAR-T therapy compared with the full database, of which 11 GAEs (n = 156, 10.28%) were associated with gastrointestinal infections (GI), such as clostridium difficile colitis (n = 44 [2.90%], ROR = 5.55), enterovirus infection (n = 23 [1.52%], ROR = 20.02), and mucormycosis (n = 15 [0.99%], ROR = 3.09). Overall, the fatality rate of 11 GI-related AEs was 29.49%, especially mucormycosis causing substantial mortality with 60%. In addition, 4 of 23 overreported GAEs were related to haemorrhage and the mortality of gastrointestinal haemorrhage was 73.17%. Lastly, 29 death-related GAEs were identified. These findings could help clinicians early alert those rarely reported but lethal GAEs, thus reducing the risk of severe toxicities.","PeriodicalId":9577,"journal":{"name":"Cancer gene therapy","volume":"31 5","pages":"710-720"},"PeriodicalIF":6.4,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140315432","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