Molecular Therapy Oncolytics最新文献_第10页

Thank you to our 2022 reviewers 感谢我们2022年的评审

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-11-25 DOI: 10.1016/j.omto.2022.11.005

引用次数: 0

The IAP antagonist birinapant enhances chimeric antigen receptor T cell therapy for glioblastoma by overcoming antigen heterogeneity. IAP拮抗剂比瑞那潘通过克服抗原异质性增强了治疗胶质母细胞瘤的嵌合抗原受体T细胞疗法。

IF 5.3 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-11-15 eCollection Date: 2022-12-15 DOI: 10.1016/j.omto.2022.11.004

Edward Z Song, Xin Wang, Benjamin I Philipson, Qian Zhang, Radhika Thokala, Logan Zhang, Charles-Antoine Assenmacher, Zev A Binder, Guo-Li Ming, Donald M O'Rourke, Hongjun Song, Michael C Milone

{"title":"The IAP antagonist birinapant enhances chimeric antigen receptor T cell therapy for glioblastoma by overcoming antigen heterogeneity.","authors":"Edward Z Song, Xin Wang, Benjamin I Philipson, Qian Zhang, Radhika Thokala, Logan Zhang, Charles-Antoine Assenmacher, Zev A Binder, Guo-Li Ming, Donald M O'Rourke, Hongjun Song, Michael C Milone","doi":"10.1016/j.omto.2022.11.004","DOIUrl":"10.1016/j.omto.2022.11.004","url":null,"abstract":"Antigen heterogeneity that results in tumor antigenic escape is one of the major obstacles to successful chimeric antigen receptor (CAR) T cell therapies in solid tumors including glioblastoma multiforme (GBM). To address this issue and improve the efficacy of CAR T cell therapy for GBM, we developed an approach that combines CAR T cells with inhibitor of apoptosis protein (IAP) antagonists, a new class of small molecules that mediate the degradation of IAPs, to treat GBM. Here, we demonstrated that the IAP antagonist birinapant could sensitize GBM cell lines and patient-derived primary GBM organoids to apoptosis induced by CAR T cell-derived cytokines, such as tumor necrosis factor. Therefore, birinapant could enhance CAR T cell-mediated bystander death of antigen-negative GBM cells, thus preventing tumor antigenic escape in antigen-heterogeneous tumor models in vitro and in vivo. In addition, birinapant could promote the activation of NF-κB signaling pathways in antigen-stimulated CAR T cells, and with a birinapant-resistant tumor model we showed that birinapant had no deleterious effect on CAR T cell functions in vitro and in vivo. Overall, we demonstrated the potential of combining the IAP antagonist birinapant with CAR T cells as a novel and feasible approach to overcoming tumor antigen heterogeneity and enhancing CAR T cell therapy for GBM.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"27 ","pages":"288-304"},"PeriodicalIF":5.3,"publicationDate":"2022-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/31/7f/main.PMC9707011.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9653037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

ScRNA-seq and bulk RNA-seq reveal the characteristics of ferroptosis and establish a risk signature in cholangiocarcinoma ScRNA-seq和bulk RNA-seq揭示了胆管癌铁下垂的特征，并建立了胆管癌的风险特征

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-09-26 DOI: 10.1016/j.omto.2022.09.008

W. Yao, Xuxu Liu, Yuanhang He, Maolan Tian, Shixin Lu, Qiang Wang, Yifeng Zheng, Zhenyi Lv, Chenjun Hao, Dongbo Xue, Xianzhi Meng

引用次数: 1

Comprehensive landscape of tRNA-derived fragments in lung cancer. 肺癌中trna衍生片段的综合景观。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-09-15 DOI: 10.1016/j.omto.2022.07.002

Zitong Gao, Mayumi Jijiwa, Masaki Nasu, Heather Borgard, Ting Gong, Jinwen Xu, Shaoqiu Chen, Yuanyuan Fu, Yu Chen, Xiamin Hu, Gang Huang, Youping Deng

{"title":"Comprehensive landscape of tRNA-derived fragments in lung cancer.","authors":"Zitong Gao, Mayumi Jijiwa, Masaki Nasu, Heather Borgard, Ting Gong, Jinwen Xu, Shaoqiu Chen, Yuanyuan Fu, Yu Chen, Xiamin Hu, Gang Huang, Youping Deng","doi":"10.1016/j.omto.2022.07.002","DOIUrl":"https://doi.org/10.1016/j.omto.2022.07.002","url":null,"abstract":"Transfer RNA (tRNA)-derived fragment (tRDF) is a novel small non-coding RNA that presents in different types of cancer. The comprehensive understanding of tRDFs in non-small cell lung cancer remains largely unknown. In this study, 1,550 patient samples of non-small cell lung cancer (NSCLC) were included, and 52 tRDFs with four subtypes were identified. Six tRDFs were picked as diagnostic signatures based on the tRDFs expression patterns, and area under the curve (AUC) in independent validations is up to 0.90. Two signatures were validated successfully in plasma samples, and six signatures confirmed the consistency of distinguished expression in NSCLC cell lines. Ten tRDFs along with independent risk scores can be used to predict survival outcomes by stages; 5a_tRF-Ile-AAT/GAT can be a prognosis biomarker for early stage. Association analysis of tRDFs-signatures-correlated mRNAs and microRNA (miRNA) were targeted to the cell cycle and oocyte meiosis signaling pathways. Five tRDFs were assessed to associate with PD-L1 immune checkpoint and correlated with the genes that target in PD-L1 checkpoint signaling pathway. Our study is the first to provide a comprehensive analysis of tRDFs in lung cancer, including four subtypes of tRDFs, investigating the diagnostic and prognostic values, and demonstrated their biological function and transcriptional role as well as potential immune therapeutic value.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"26 ","pages":"207-225"},"PeriodicalIF":5.7,"publicationDate":"2022-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/92/75/main.PMC9307607.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10429101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 10

Azelnidipine inhibits esophageal squamous cell carcinoma proliferation in vivo and in vitro by targeting MEK1/2 阿泽尼地平通过靶向MEK1/2抑制食管鳞状细胞癌的体内外增殖

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-09-01 DOI: 10.1016/j.omto.2022.09.007

Lili Zhao, Yuhan Zhang, Ang Li, Xuebo Lu, Mingzhu li, Qi Yuan, N. Yang, Xiaokun Zhao, Xin Li, Yanan Jiang, Kangdong Liu

引用次数: 4

Reinvigoration of innate and adaptive immunity via therapeutic cellular vaccine for patients with AML 通过治疗性细胞疫苗对AML患者的先天性和适应性免疫的重新激活

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-09-01 DOI: 10.1016/j.omto.2022.09.001

S. Fujii, T. Kawamata, K. Shimizu, J. Nakabayashi, S. Yamasaki, T. Iyoda, J. Shinga, H. Nakazato, Ann Sanpei, Masami Kawamura, S. Ueda, J. Dörrie, S. Mojsov, M. Dhodapkar, M. Hidaka, Masanori Nojima, F. Nagamura, S. Yoshida, Toshio Goto, A. Tojo

引用次数: 6

Perturbing DDR signaling enhances cytotoxic effects of local oncolytic virotherapy and modulates the immune environment in glioma. 干扰DDR信号转导可增强局部溶瘤病毒疗法的细胞毒性效应，并调节胶质瘤的免疫环境。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-07-31 eCollection Date: 2022-09-15 DOI: 10.1016/j.omto.2022.07.009

Marilin S Koch, Mykola Zdioruk, Michal O Nowicki, Alec M Griffith, Estuardo Aguilar-Cordova, Laura K Aguilar, Brian W Guzik, Francesca Barone, Paul Peter Tak, Katharina Schregel, Michael S Hoetker, James A Lederer, E Antonio Chiocca, Ghazaleh Tabatabai, Sean E Lawler

{"title":"Perturbing DDR signaling enhances cytotoxic effects of local oncolytic virotherapy and modulates the immune environment in glioma.","authors":"Marilin S Koch, Mykola Zdioruk, Michal O Nowicki, Alec M Griffith, Estuardo Aguilar-Cordova, Laura K Aguilar, Brian W Guzik, Francesca Barone, Paul Peter Tak, Katharina Schregel, Michael S Hoetker, James A Lederer, E Antonio Chiocca, Ghazaleh Tabatabai, Sean E Lawler","doi":"10.1016/j.omto.2022.07.009","DOIUrl":"10.1016/j.omto.2022.07.009","url":null,"abstract":"CAN-2409 is a replication-deficient adenovirus encoding herpes simplex virus (HSV) thymidine kinase (tk) currently in clinical trials for treatment of glioblastoma. The expression of tk in transduced cancer cells results in conversion of the pro-drug ganciclovir into a toxic metabolite causing DNA damage, inducing immunogenic cell death and immune activation. We hypothesize that CAN-2409 combined with DNA-damage-response inhibitors could amplify tumor cell death, resulting in an improved response. We investigated the effects of ATR inhibitor AZD6738 in combination with CAN-2409 in vitro using cytotoxicity, cytokine, and fluorescence-activated cell sorting (FACS) assays in glioma cell lines and in vivo with an orthotopic syngeneic murine glioma model. Tumor immune infiltrates were analyzed by cytometry by time of flight (CyTOF). In vitro, we observed a significant increase in the DNA-damage marker γH2AX and decreased expression of PD-L1, pro-tumorigenic cytokines (interleukin-1β [IL-1β], IL-4), and ligand NKG2D after combination treatment compared with monotherapy or control. In vivo, long-term survival was increased after combination treatment (66.7%) compared with CAN-2409 (50%) and control. In a tumor re-challenge, long-term immunity after combination treatment was not improved. Our results suggest that ATR inhibition could amplify CAN-2409's efficacy in glioblastoma through increased DNA damage while having complex immunological ramifications, warranting further studies to determine the ideal conditions for maximized therapeutic benefit.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"26 ","pages":"275-288"},"PeriodicalIF":5.7,"publicationDate":"2022-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/87/25/main.PMC9391522.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9659033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Retraction Notice to: Exosomes Carrying MicroRNA-155 Target Forkhead Box O3 of Endothelial Cells and Promote Angiogenesis in Gastric Cancer. 关于携带MicroRNA-155的外泌体靶向内皮细胞叉头盒O3并促进胃癌血管生成的撤回通知。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-06-16 DOI: 10.1016/j.omto.2022.05.001

Yi Dong, Cheng Qian, Guangming Wan, Panshi Yan, Shenzhi Liang, Jiong Wang

引用次数: 1

Erratum: Ablation of Stromal Cells with a Targeted Proapoptotic Peptide Suppresses Cancer Chemotherapy Resistance and Metastasis. 勘误:靶向促凋亡肽消融基质细胞可抑制肿瘤化疗耐药和转移。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-06-16 DOI: 10.1016/j.omto.2022.05.007

Fei Su, Xiaoping Wang, T. Pearson, Jangsoon Lee, S. Krishnamurthy, N. Ueno, M. Kolonin

引用次数: 0

Spatiotemporal analysis of induced neural stem cell therapy to overcome advanced glioblastoma recurrence. 诱导神经干细胞治疗克服晚期胶质母细胞瘤复发的时空分析。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-06-07 eCollection Date: 2022-09-15 DOI: 10.1016/j.omto.2022.06.004

Andrew B Satterlee, Denise E Dunn, Alain Valdivia, Daniel Malawsky, Andrew Buckley, Timothy Gershon, Scott Floyd, Shawn Hingtgen

{"title":"Spatiotemporal analysis of induced neural stem cell therapy to overcome advanced glioblastoma recurrence.","authors":"Andrew B Satterlee, Denise E Dunn, Alain Valdivia, Daniel Malawsky, Andrew Buckley, Timothy Gershon, Scott Floyd, Shawn Hingtgen","doi":"10.1016/j.omto.2022.06.004","DOIUrl":"10.1016/j.omto.2022.06.004","url":null,"abstract":"Genetically engineered neural stem cells (NSCs) are a promising therapy for the highly aggressive brain cancer glioblastoma (GBM); however, treatment durability remains a major challenge. We sought to define the events that contribute to dynamic adaptation of GBM during treatment with human skin-derived induced NSCs releasing the pro-apoptotic agent TRAIL (iNSC-TRAIL) and develop strategies that convert initial tumor kill into sustained GBM suppression. In vivo and ex vivo analysis before, during, and after treatment revealed significant shifts in tumor transcriptome and spatial distribution as the tumors adapted to treatment. To address this, we designed iNSC delivery strategies that increased spatiotemporal TRAIL coverage and significantly decreased GBM volume throughout the brain, reducing tumor burden 100-fold as quantified in live ex vivo brain slices. The varying impact of different strategies on treatment durability and median survival of both solid and invasive tumors provides important guidance for optimizing iNSC therapy.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"26 ","pages":"49-62"},"PeriodicalIF":5.7,"publicationDate":"2022-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ef/99/main.PMC9217992.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10760715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: 1