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

Azelnidipine may be a valuable drug for chemoprevention of ESCC with high MEK1/2 levels. 阿泽尼地平可能是一种有价值的药物，用于高MEK1/2水平ESCC的化学预防。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-11-16 eCollection Date: 2022-12-15 DOI: 10.1016/j.omto.2022.10.008

Haili Qian

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

A cross-reactive pH-dependent EGFR antibody with improved tumor selectivity and penetration obtained by structure-guided engineering. 通过结构引导工程获得了一种具有提高肿瘤选择性和穿透性的交叉反应性ph依赖性EGFR抗体。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-11-13 eCollection Date: 2022-12-15 DOI: 10.1016/j.omto.2022.11.001

Ximing Liu, Xinxin Tian, Xinyan Hao, Huixiang Zhang, Kailun Wang, Zhizhong Wei, Xin Wei, Yulu Li, Jianhua Sui

{"title":"A cross-reactive pH-dependent EGFR antibody with improved tumor selectivity and penetration obtained by structure-guided engineering.","authors":"Ximing Liu, Xinxin Tian, Xinyan Hao, Huixiang Zhang, Kailun Wang, Zhizhong Wei, Xin Wei, Yulu Li, Jianhua Sui","doi":"10.1016/j.omto.2022.11.001","DOIUrl":"https://doi.org/10.1016/j.omto.2022.11.001","url":null,"abstract":"The clinical use of anti-EGFR antibody-based cancer therapy has been limited by antibody-EGFR binding in normal tissues, so developing pH-dependent anti-EGFR antibodies that selectively bind with EGFR in tumors-by taking advantage of the acidity of tumor microenvironment relative to normal tissues-may overcome these limitations. Here, we generated pH-dependent anti-EGFR antibodies with cross-species reactivity for human and mouse EGFR, and we demonstrate that pH-dependent antibodies exhibit tumor-selective binding by binding strongly to EGFR under acidic conditions (pH 6.5) but binding weakly under neutral (pH 7.4) conditions. Based on screening a non-immune human antibody library and antibody affinity maturation, we initially generated antibodies with cross-species reactivity for human and mouse EGFR. A structure model was subsequently constructed and interrogated for hotspots affecting pH-dependent binding, which supported development of a cross-reactive pH-dependent anti-EGFR antibody, G532. Compared with its non-pH-dependent antibody variant, G532 exhibits improved tumor selectivity, tumor penetration, and antitumor activity. Thus, beyond showing that pH-dependent anti-EGFR antibodies can overcome multiple limitations with antibody-based cancer therapies targeting EGFR, our study illustrates a structure-guided antibody-antigen binding pH-dependency engineering strategy to enhance antibody tumor selectivity and tumor penetration, which can inform the future development of antibody-based cancer therapies targeting other ubiquitously expressed molecules.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":" ","pages":"256-269"},"PeriodicalIF":5.7,"publicationDate":"2022-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/20/de/main.PMC9703009.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40457041","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: 2

Novel insights into circular RNA regulation in arsenic-exposure-induced lung cancer. 砷暴露诱导肺癌中环状RNA调控的新见解。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-11-12 eCollection Date: 2022-12-15 DOI: 10.1016/j.omto.2022.10.010

Xiang Ao, Ying Liu

引用次数: 4

Exploring the potential of eRNAs in cancer immunotherapy. 探索erna在癌症免疫治疗中的潜力。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-11-08 eCollection Date: 2022-12-15 DOI: 10.1016/j.omto.2022.10.009

Lianxiang Luo, Xinming Chen

引用次数: 0

Ferroptosis gene signature in cholangiocarcinoma. 胆管癌中铁下垂基因特征。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-11-08 eCollection Date: 2022-12-15 DOI: 10.1016/j.omto.2022.10.007

Pradeep Reddy Cingaram

引用次数: 0

PROTACs in gastrointestinal cancers. 胃肠道癌症中的PROTACs。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-11-03 eCollection Date: 2022-12-15 DOI: 10.1016/j.omto.2022.10.012

Yu Chen, Qingfan Yang, Jinrun Xu, Liyao Tang, Yan Zhang, Fukuan Du, Yueshui Zhao, Xu Wu, Mingxing Li, Jing Shen, Ruilin Ding, Hongying Cao, Wanping Li, Xiaobing Li, Meijuan Chen, Zhigui Wu, Chi Hin Cho, Yu Du, Qinglian Wen, Zhangang Xiao

{"title":"PROTACs in gastrointestinal cancers.","authors":"Yu Chen, Qingfan Yang, Jinrun Xu, Liyao Tang, Yan Zhang, Fukuan Du, Yueshui Zhao, Xu Wu, Mingxing Li, Jing Shen, Ruilin Ding, Hongying Cao, Wanping Li, Xiaobing Li, Meijuan Chen, Zhigui Wu, Chi Hin Cho, Yu Du, Qinglian Wen, Zhangang Xiao","doi":"10.1016/j.omto.2022.10.012","DOIUrl":"https://doi.org/10.1016/j.omto.2022.10.012","url":null,"abstract":"Proteolysis targeting chimera (PROTAC) presents a powerful strategy for targeted protein degradation (TPD). The heterobifunctional PROTAC molecule consists of an E3 ligase ligand covalently linked to a protein of interest (POI) via a linker. PROTAC can induce ubiquitinated proteasomal degradation of proteins by hijacking the ubiquitin-proteasome degradation system (UPS). This technique has the advantages of broad targeting profile, good cell permeability, tissue specificity, high selectivity, oral bioavailability, and controllability. To date, a growing number of PROTACs targeting gastrointestinal cancers have been successfully developed, and, in many cases, their POIs have been validated as clinical drug targets. To the best of our knowledge, 15 PROTACs against various targets are currently tested in clinical trials, and many more are likely to be added in the near future. Therefore, this paper details the mechanism, research progress, and application in clinical trials of PROTACs, and summarizes the research achievements related to PROTACs in gastrointestinal cancers. Finally, we discuss the advantages and potential challenges of PROTAC for cancer treatment.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":" ","pages":"204-223"},"PeriodicalIF":5.7,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/26/1d/main.PMC9676279.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40702878","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: 6

Dual EGFR- and TfR-targeted gene transfer for sodium iodide symporter gene therapy of glioblastoma. EGFR和tfr双重靶向基因转移治疗胶质母细胞瘤的碘化钠同转运体基因。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-11-03 eCollection Date: 2022-12-15 DOI: 10.1016/j.omto.2022.10.013

Rebekka Spellerberg, Teoman Benli-Hoppe, Carolin Kitzberger, Mara Hageneier, Nathalie Schwenk, Özgür Öztürk, Katja Steiger, Gabriele Multhoff, Matthias Eiber, Franz Schilling, Wolfgang A Weber, Roland E Kälin, Rainer Glass, Peter J Nelson, Ernst Wagner, Christine Spitzweg

{"title":"Dual EGFR- and TfR-targeted gene transfer for sodium iodide symporter gene therapy of glioblastoma.","authors":"Rebekka Spellerberg, Teoman Benli-Hoppe, Carolin Kitzberger, Mara Hageneier, Nathalie Schwenk, Özgür Öztürk, Katja Steiger, Gabriele Multhoff, Matthias Eiber, Franz Schilling, Wolfgang A Weber, Roland E Kälin, Rainer Glass, Peter J Nelson, Ernst Wagner, Christine Spitzweg","doi":"10.1016/j.omto.2022.10.013","DOIUrl":"https://doi.org/10.1016/j.omto.2022.10.013","url":null,"abstract":"Sodium iodide symporter (NIS) gene transfer for active accumulation of iodide in tumor cells is a powerful theranostic strategy facilitating both diagnostic and therapeutic application of radioiodide. In glioblastoma (GBM), the blood-brain barrier (BBB) presents an additional delivery barrier for nucleic acid nanoparticles. In the present study, we designed dual-targeted NIS plasmid DNA complexes containing targeting ligands for the transferrin receptor (TfR) and the epidermal growth factor receptor (EGFR), thus providing the potential for active transport across the BBB followed by targeting of tumor cells. In vitro 125I transfection studies confirmed TfR- and EGFR-dependent transfection efficiency and NIS-specific iodide uptake of dual-targeted polyplexes. In vivo gene transfer in mice bearing orthotopic U87 GBM xenografts was assessed at 48 h after intravenous polyplex injection by positron emission tomography (PET) imaging using 18F-labeled tetrafluoroborate (TFB) as tracer. The tumoral 18F-TFB uptake of mice treated with dual-targeted polyplexes (0.56% ± 0.08% ID/mL) was significantly higher compared with mice treated with EGFR-mono-targeted (0.33% ± 0.03% ID/mL) or TfR-mono-targeted (0.27% ± 0.04% ID/mL) polyplexes. In therapy studies, application of 131I induced a superior therapeutic effect of the dual-targeted therapy, demonstrated by a significant delay in tumor growth and prolonged survival.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":" ","pages":"272-287"},"PeriodicalIF":5.7,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3b/f0/main.PMC9709165.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40557002","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: 3

Gene-edited and CAR-NK cells: Opportunities and challenges with engineering of NK cells for immunotherapy. 基因编辑和CAR-NK细胞:NK细胞工程用于免疫治疗的机遇和挑战。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2022-11-03 eCollection Date: 2022-12-15 DOI: 10.1016/j.omto.2022.10.011

Xinyu Wu, Sandro Matosevic

{"title":"Gene-edited and CAR-NK cells: Opportunities and challenges with engineering of NK cells for immunotherapy.","authors":"Xinyu Wu, Sandro Matosevic","doi":"10.1016/j.omto.2022.10.011","DOIUrl":"https://doi.org/10.1016/j.omto.2022.10.011","url":null,"abstract":"Treatment of many cancers, particularly those that remain difficult to treat or are refractive after standard-of-care therapies, has been challenging with cell-based therapies. Although relatively safe as allogeneic therapies and innately effective against cancers without the need for antigen sensitization, natural killer (NK) cells have necessitated use of genetic manipulation approaches to enhance their specificity, persistence, and homing. Chimeric antigen receptor (CAR) and gene-edited NK cell therapies have emerged as a potent treatment modality, addressing many of the issues that have plagued such gene-based therapies with other cell types. Early examples of engineered NK cell therapies have largely leveraged their activity against hematological malignancies in combination with conventional construct architectures or by editing putative genetic targets of immunosuppression. As the motivation to tackle more complex solid tumors grows, so has the sophistication and emergence of NK-specific constructs and engineering approaches. Multi-CARs, combinations with diverse genome editing technologies, as well as responsive and sensing CARs have appeared in the context of NK cell therapy. Here we discuss engineering approaches for NK cell therapy, the latest developments in the field, and what stands in the way of those promises en route to clinical translation.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":" ","pages":"224-238"},"PeriodicalIF":5.7,"publicationDate":"2022-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4d/78/main.PMC9676278.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40702880","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: 3