Molecular Therapy Oncolytics最新文献_第7页

Oncolytic viruses: Narcissistic or altruistic arsonists? 溶瘤病毒：自恋还是无私的纵火犯？

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-04-26 eCollection Date: 2023-06-15 DOI: 10.1016/j.omto.2023.04.002

Luke Kendall, Richard G Vile

引用次数: 0

oHSV-P10 reduces glioma stem cell enrichment after oncolytic HSV therapy. oHSV-P10 可减少溶瘤 HSV 治疗后胶质瘤干细胞的富集。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-04-03 eCollection Date: 2023-06-15 DOI: 10.1016/j.omto.2023.03.003

Upasana Sahu, Matthew P Mullarkey, Guangsheng Pei, Zhongming Zhao, Bangxing Hong, Balveen Kaur

引用次数: 0

Disruption of CISH promotes the antitumor activity of human T cells and decreases PD-1 expression levels. 破坏CISH可促进人T细胞抗肿瘤活性，降低PD-1表达水平。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2022.12.003

Jiang Lv, Le Qin, Ruocong Zhao, Di Wu, Zhiping Wu, Diwei Zheng, Siyu Li, Mintao Luo, Qiting Wu, Youguo Long, Zhaoyang Tang, Yan-Lai Tang, Xuequn Luo, Yao Yao, Li-Hua Yang, Peng Li

{"title":"Disruption of CISH promotes the antitumor activity of human T cells and decreases PD-1 expression levels.","authors":"Jiang Lv, Le Qin, Ruocong Zhao, Di Wu, Zhiping Wu, Diwei Zheng, Siyu Li, Mintao Luo, Qiting Wu, Youguo Long, Zhaoyang Tang, Yan-Lai Tang, Xuequn Luo, Yao Yao, Li-Hua Yang, Peng Li","doi":"10.1016/j.omto.2022.12.003","DOIUrl":"https://doi.org/10.1016/j.omto.2022.12.003","url":null,"abstract":"Tumor cells and the immunosuppressive tumor microenvironment suppress the antitumor activity of T cells through immune checkpoints, including the PD-L1/PD-1 axis. Cytokine-inducible SH2-containing protein (CISH), a member of the suppressor of cytokine signaling (SOCS) family, inhibits JAK-STAT and T cell receptor (TCR) signaling in T and natural killer (NK) cells. However, its role in the regulation of immune checkpoints in T cells remains unclear. In this study, we ablated CISH in T cells with CRISPR-Cas9 and found that the sensitivity of T cells to TCR and cytokine stimulation was increased. In addition, chimeric antigen receptor T cells with CISH deficiency exhibited longer survival and higher cytokine secretion and antitumor activity. Notably, PD-1 expression was decreased in activated CISH-deficient T cells in vitro and in vivo. The level of FBXO38, a ubiquitination-regulating protein that reduces PD-1 expression, was elevated in activated T cells after CISH ablation. Hence, this study reveals a mechanism by which CISH promotes PD-1 expression by suppressing the expression of FBXO38 and proposes a new strategy for augmenting the therapeutic effect of CAR-T cells by inhibiting CISH.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"28 ","pages":"46-58"},"PeriodicalIF":5.7,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/11/b0/main.PMC9827364.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9100293","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: 4

Sodium iodide symporter-targeted gene therapy in glioblastoma. 碘化钠同调蛋白靶向基因治疗胶质母细胞瘤。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2022.12.004

Juan Pablo Nicola, Christopher J LaRocca

引用次数: 0

Oncolytic adenovirus coding for bispecific T cell engager against human MUC-1 potentiates T cell response against solid tumors. 针对人MUC-1的双特异性T细胞接合器编码的溶瘤腺病毒增强了T细胞对实体肿瘤的反应。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2022.12.007

Saru Basnet, Joao M Santos, Dafne C A Quixabeira, James H A Clubb, Susanna A M Grönberg-Vähä-Koskela, Victor Arias, Santeri Pakola, Tatiana V Kudling, Camilla Heiniö, Riikka Havunen, Victor Cervera-Carrascon, Suvi Sorsa, Marjukka Anttila, Anna Kanerva, Akseli Hemminki

{"title":"Oncolytic adenovirus coding for bispecific T cell engager against human MUC-1 potentiates T cell response against solid tumors.","authors":"Saru Basnet, Joao M Santos, Dafne C A Quixabeira, James H A Clubb, Susanna A M Grönberg-Vähä-Koskela, Victor Arias, Santeri Pakola, Tatiana V Kudling, Camilla Heiniö, Riikka Havunen, Victor Cervera-Carrascon, Suvi Sorsa, Marjukka Anttila, Anna Kanerva, Akseli Hemminki","doi":"10.1016/j.omto.2022.12.007","DOIUrl":"https://doi.org/10.1016/j.omto.2022.12.007","url":null,"abstract":"Immunotherapy with bispecific T cell engagers has shown efficacy in patients with hematologic malignancies and uveal melanoma. Antitumor effects of bispecific T cell engagers in most solid tumors are limited due to their short serum half-life and insufficient tumor concentration. We designed a novel serotype 5/3 oncolytic adenovirus encoding a human mucin1 antibody and the human CD3 receptor, Ad5/3-E2F-d24-aMUC1aCD3 (TILT-321). TILT-321 is engineered to replicate only in cancer cells, leading to a high concentration of the aMUC1aCD3 molecule in the tumor microenvironment. Infection and cell viability assays were performed to determine the oncolytic potential of the novel construct. The functionality of the virus-derived aMUC1aCD3 was evaluated in vitro. When TILT-321 was combined with allogeneic T cells, rapid tumor cell lysis was observed. TILT-321-infected cells secreted functional aMUC1aCD3, as shown by increased T cell activity and its binding to MUC1 and CD3. In vivo, TILT-321 treatment led to effective antitumor efficacy mediated by increased intratumoral T cell activity in an A549 and patient-derived ovarian cancer xenograft mouse model humanized with peripheral blood mononuclear cells (PBMC). This study provides a proof of concept for an effective strategy to overcome the key limitations of recombinant bispecific T cell engager delivery for solid tumor treatment.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"28 ","pages":"59-73"},"PeriodicalIF":5.7,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/00/main.PMC9842968.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9178066","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

Characterization and quantitation of busulfan DNA adducts in the blood of patients receiving busulfan therapy. 接受布苏芬治疗的患者血液中布苏芬DNA加合物的表征和定量。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2023.01.005

Valeria Guidolin, Yupeng Li, Foster C Jacobs, Margaret L MacMillan, Peter W Villalta, Stephen S Hecht, Silvia Balbo

{"title":"Characterization and quantitation of busulfan DNA adducts in the blood of patients receiving busulfan therapy.","authors":"Valeria Guidolin, Yupeng Li, Foster C Jacobs, Margaret L MacMillan, Peter W Villalta, Stephen S Hecht, Silvia Balbo","doi":"10.1016/j.omto.2023.01.005","DOIUrl":"https://doi.org/10.1016/j.omto.2023.01.005","url":null,"abstract":"DNA alkylating drugs have been used as cancer chemotherapy with variable outcomes. The establishment of predictive biomarkers to identify patients who will effectively respond to treatment would allow for the development of personalized therapies. As the degree of interaction of alkylating drug with DNA plays a key role in their mechanism of action, our hypothesis is that the measurement of the DNA adducts formed by alkylating drugs could be used to inform patient stratification. Beginning with busulfan, we took advantage of our DNA adductomic approach to characterize DNA adducts formed by reacting busulfan with calf-thymus DNA. Samples collected from six patients undergoing busulfan-based chemotherapy prior to allogeneic hematopoietic cell transplantation were analyzed for the presence of busulfan-derived DNA adducts. Among the 15 adducts detected in vitro, 12 were observed in the patient blood confirming the presence of a large profile of DNA adducts in vivo. Two of the detected adducts were structurally confirmed by comparison with synthetic standards and quantified in patients. These data confirm our ability to comprehensively characterize busulfan-derived DNA damage and set the stage for the development of methods to support personalized chemotherapy.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"28 ","pages":"197-210"},"PeriodicalIF":5.7,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6e/2a/main.PMC9938526.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9493813","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

R. Daniel Beauchamp (1946-2022). R.丹尼尔·比彻姆(1946-2022)。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2023.01.004

引用次数: 0

Mechanisms of drug resistance in breast cancer liver metastases: Dilemmas and opportunities. 乳腺癌肝转移的耐药机制:困境与机遇。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2023.02.001

Chun-Yan Yan, Meng-Lu Zhao, Ya-Nan Wei, Xi-He Zhao

引用次数: 1

A cancer cell membrane coated, doxorubicin and microRNA co-encapsulated nanoplatform for colorectal cancer theranostics. 肿瘤细胞膜包被、阿霉素和microRNA共包被的结直肠癌治疗纳米平台。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2022.12.002

Sihao Zhu, Ziyuan Li, Dongye Zheng, Yue Yu, Jing Xiang, Xiao Ma, Dongqing Xu, Jiajun Qiu, Ziyu Yang, Zhiyi Wang, Jun Li, Hongfang Sun, Weiqiang Chen, Xiangxi Meng, Yanye Lu, Qiushi Ren

{"title":"A cancer cell membrane coated, doxorubicin and microRNA co-encapsulated nanoplatform for colorectal cancer theranostics.","authors":"Sihao Zhu, Ziyuan Li, Dongye Zheng, Yue Yu, Jing Xiang, Xiao Ma, Dongqing Xu, Jiajun Qiu, Ziyu Yang, Zhiyi Wang, Jun Li, Hongfang Sun, Weiqiang Chen, Xiangxi Meng, Yanye Lu, Qiushi Ren","doi":"10.1016/j.omto.2022.12.002","DOIUrl":"https://doi.org/10.1016/j.omto.2022.12.002","url":null,"abstract":"Endogenous microRNAs (miRNA) in tumors are currently under exhaustive investigation as potential therapeutic agents for cancer treatment. Nevertheless, RNase degradation, inefficient and untargeted delivery, limited biological effect, and currently unclear side effects remain unsettled issues that frustrate clinical application. To address this, a versatile targeted delivery system for multiple therapeutic and diagnostic agents should be adapted for miRNA. In this study, we developed membrane-coated PLGA-b-PEG DC-chol nanoparticles (m-PPDCNPs) co-encapsulating doxorubicin (Dox) and miRNA-190-Cy7. Such a system showed low biotoxicity, high loading efficiency, and superior targeting ability. Systematic delivery of m-PPDCNPs in mouse models showed exceptionally specific tumor accumulation. Sustained release of miR-190 inhibited tumor angiogenesis, tumor growth, and migration by regulating a large group of angiogenic effectors. Moreover, m-PPDCNPs also enhanced the sensitivity of Dox by suppressing TGF-β signal in colorectal cancer cell lines and mouse models. Together, our results demonstrate a stimulating and promising m-PPDCNPs nanoplatform for colorectal cancer theranostics.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"28 ","pages":"182-196"},"PeriodicalIF":5.7,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9937835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9317499","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

Targeting receptor tyrosine kinases in ovarian cancer: Genomic dysregulation, clinical evaluation of inhibitors, and potential for combinatorial therapies. 靶向受体酪氨酸激酶在卵巢癌:基因组失调，抑制剂的临床评估，和潜在的联合治疗。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2023.02.006

Ying Wei, Sonia Erfani, David Schweer, Rafael de Gouvea, Javeria Qadir, Junfeng Shi, Kai Cheng, Dabao Wu, Rolf Craven, Yadi Wu, Thibault Olivier, Lauren A Baldwin, Binhua Zhou, Ying Zhou, Weidong Zhao, Burton B Yang, Frederick R Ueland, Xiuwei H Yang

{"title":"Targeting receptor tyrosine kinases in ovarian cancer: Genomic dysregulation, clinical evaluation of inhibitors, and potential for combinatorial therapies.","authors":"Ying Wei, Sonia Erfani, David Schweer, Rafael de Gouvea, Javeria Qadir, Junfeng Shi, Kai Cheng, Dabao Wu, Rolf Craven, Yadi Wu, Thibault Olivier, Lauren A Baldwin, Binhua Zhou, Ying Zhou, Weidong Zhao, Burton B Yang, Frederick R Ueland, Xiuwei H Yang","doi":"10.1016/j.omto.2023.02.006","DOIUrl":"https://doi.org/10.1016/j.omto.2023.02.006","url":null,"abstract":"Epithelial ovarian cancer (EOC) remains one of the leading causes of cancer-related deaths among women worldwide. Receptor tyrosine kinases (RTKs) have long been sought as therapeutic targets for EOC, as they are frequently hyperactivated in primary tumors and drive disease relapse, progression, and metastasis. More recently, these oncogenic drivers have been implicated in EOC response to poly(ADP-ribose) polymerase (PARP) inhibitors and epigenome-interfering agents. This evidence revives RTKs as promising targets for therapeutic intervention of EOC. This review summarizes recent studies on the role of RTKs in EOC malignancy and the use of their inhibitors for clinical treatment. Our focus is on the ERBB family, c-Met, and VEGFR, as they are linked to drug resistance and targetable using commercially available drugs. The importance of these RTKs and their inhibitors is highlighted by their impact on signal transduction and intratumoral heterogeneity in EOC and successful use as maintenance therapy in the clinic through suppression of the VEGF/VEGFR axis. Finally, the therapeutic potential of RTK inhibitors is discussed in the context of combinatorial targeting via co-inhibiting proliferative and anti-apoptotic pathways, epigenomic/transcriptional programs, and harnessing the efficacy of PARP inhibitors and programmed cell death 1/ligand 1 immune checkpoint therapies.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"28 ","pages":"293-306"},"PeriodicalIF":5.7,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d1/2a/main.PMC9999170.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9775616","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