Molecular therapy. Oncology最新文献_第5页

Bile molecular landscape provides pathological insight and classifies signatures predictive of carcinoma of the gall bladder. 胆汁分子景观提供病理洞察和分类特征预测胆囊癌。

Molecular therapy. Oncology Pub Date : 2024-11-06 eCollection Date: 2024-12-19 DOI: 10.1016/j.omton.2024.200904

Nupur Sharma, Sadam H Bhat, Babu Mathew, Manisha Yadav, Gaurav Tripathi, Vasundhra Bindal, Sanju Yadav, Neha Sharma, Sushmita Pandey, Hami Hemati, Deepika Bohra, Rashmi Rana, Narendra Kumar Sharma, Sanyam Falari, Viniyendra Pamecha, Jaswinder Singh Maras

{"title":"Bile molecular landscape provides pathological insight and classifies signatures predictive of carcinoma of the gall bladder.","authors":"Nupur Sharma, Sadam H Bhat, Babu Mathew, Manisha Yadav, Gaurav Tripathi, Vasundhra Bindal, Sanju Yadav, Neha Sharma, Sushmita Pandey, Hami Hemati, Deepika Bohra, Rashmi Rana, Narendra Kumar Sharma, Sanyam Falari, Viniyendra Pamecha, Jaswinder Singh Maras","doi":"10.1016/j.omton.2024.200904","DOIUrl":"10.1016/j.omton.2024.200904","url":null,"abstract":"Carcinoma of the gall bladder (CAGB) has a poor prognosis. Molecular analysis of bile could classify indicators of CAGB. Bile samples (n = 87; training cohort) were screened for proteomics and metabolomics signatures of cancer detection. In bile, CAGB showed distinct proteomic (217 upregulated, 258 downregulated) and metabolomic phenotypes (111 upregulated, 505 downregulated, p < 0.05, fold change > 1.5, false discovery rate <0.01) linked to significantly increased inflammation (coagulation, arachidonic acid, bile acid) and alternate energy pathways (pentose-phosphate pathway, amino acids, lipid metabolism); and decreased glycolysis, cholesterol metabolism, PPAR, RAS, and RAP1 signaling, oxidative phosphorylation, and others compared to gallstone or healthy controls (p < 0.05). Bile proteins/metabolites signatures showed significant correlation (r 2 > 0.5, p < 0.05) with clinical parameters. Metabolite/protein signature-based probability of detection for CAGB (cancer) was >90% (p < 0.05), with area under the receiver operating characteristic curve >0.94. Validation of the top four metabolites-toluene, 5,6-DHET, creatine, and phenylacetaldehyde-in separate cohorts (n = 80; bile [T1] and paired plasma [T2]) showed accuracy (99%) and sensitivity/specificity (>98%) for CAGB detection. Tissue validation showed bile 5,6-DHET positively correlated with tissue PCNA (proliferation), and caspase-3 linked to cancer development (r 2 >0.5, p < 0.05). In conclusion, the bile molecular landscape provides critical molecular understanding and outlines metabolomic indicator panels for early CAGB detection.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"32 4","pages":"200904"},"PeriodicalIF":0.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IL-12 encoding oNDV synergizes with CAR-T cells in orthotopic models of non-small cell lung cancer. 编码oNDV的IL-12在非小细胞肺癌原位模型中与CAR-T细胞协同作用

Molecular therapy. Oncology Pub Date : 2024-10-28 eCollection Date: 2024-12-19 DOI: 10.1016/j.omton.2024.200899

Amanda Rosewell Shaw, Daisuke Morita, Caroline E Porter, Eric Tu, Greyson W Biegert, Sonia Agrawal, Nicholas Durham, Malcolm K Brenner, Masataka Suzuki

{"title":"IL-12 encoding oNDV synergizes with CAR-T cells in orthotopic models of non-small cell lung cancer.","authors":"Amanda Rosewell Shaw, Daisuke Morita, Caroline E Porter, Eric Tu, Greyson W Biegert, Sonia Agrawal, Nicholas Durham, Malcolm K Brenner, Masataka Suzuki","doi":"10.1016/j.omton.2024.200899","DOIUrl":"10.1016/j.omton.2024.200899","url":null,"abstract":"Systemic administration of oncolytic viruses (OVs) is a promising approach for targeting metastatic solid tumors, but their anti-tumor activity is limited by pre-existing neutralizing antibodies against common human viruses. Therefore, investigators have developed OVs derived from non-human host viruses. Successful implementation of this strategy requires that the viral vector selectively infects and replicates within human cancer cells. Newcastle disease virus (NDV) is an avian paramyxovirus that, as NDV-based OVs (oNDVs), has demonstrated safety and activity against multiple human tumors in clinical trials. Their use as a single agent, however, is insufficient to cure tumors. Similarly, chimeric antigen receptor-modified T cells (CAR-T cells) enable systemic targeting of cancer cells but have limited anti-tumor effects against bulky solid tumors, in part due to the immunosuppressive tumor environment. In this study, we evaluated the anti-tumor effects of combining systemic oNDV and CAR-T cell treatments. In models of non-small cell lung carcinoma (NSCLC), we found that oNDV itself and interleukin (IL)-12 derived from oNDVs enhance HER2-directed CAR-T cell anti-tumor activity and persistence in vitro and in vivo, leading to superior control of NSCLC tumors compared with either agent alone in vivo. Our data indicate that oNDV enhances the anti-tumor effects of HER2.CAR-T cells, thus controlling the growth of orthotopic NSCLC tumors.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"32 4","pages":"200899"},"PeriodicalIF":0.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Senescence-associated secretory phenotype regulation by dual-drug delivery biomimetic nanoplatform for enhanced tumor chemotherapy. 双药传递仿生纳米平台增强肿瘤化疗的衰老相关分泌表型调节。

Molecular therapy. Oncology Pub Date : 2024-10-10 eCollection Date: 2024-12-19 DOI: 10.1016/j.omton.2024.200869

Ajay Prakash, Travis Gates, Emil Lou

引用次数: 0

Trabectedin promotes oncolytic virus antitumor efficacy, viral gene expression, and immune effector function in models of bone sarcoma. 曲贝替丁（Trabectedin）可促进溶瘤病毒在骨肉瘤模型中的抗肿瘤疗效、病毒基因表达和免疫效应功能。

Molecular therapy. Oncology Pub Date : 2024-09-26 eCollection Date: 2024-12-19 DOI: 10.1016/j.omton.2024.200886

Emily M Ringwalt, Mark A Currier, Andrea M Glaspell, Chun-Yu Chen, Matthew V Cannon, Maren Cam, Amy C Gross, Matthew Gust, Pin-Yi Wang, Louis Boon, Laura E Biederman, Emily Schwarz, Prajwal Rajappa, Dean A Lee, Elaine R Mardis, William E Carson, Ryan D Roberts, Timothy P Cripe

{"title":"Trabectedin promotes oncolytic virus antitumor efficacy, viral gene expression, and immune effector function in models of bone sarcoma.","authors":"Emily M Ringwalt, Mark A Currier, Andrea M Glaspell, Chun-Yu Chen, Matthew V Cannon, Maren Cam, Amy C Gross, Matthew Gust, Pin-Yi Wang, Louis Boon, Laura E Biederman, Emily Schwarz, Prajwal Rajappa, Dean A Lee, Elaine R Mardis, William E Carson, Ryan D Roberts, Timothy P Cripe","doi":"10.1016/j.omton.2024.200886","DOIUrl":"10.1016/j.omton.2024.200886","url":null,"abstract":"We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though the mechanism remained to be elucidated. Here we report trabectedin disrupts the intrinsic cellular antiviral response which increases viral transcript presence in the human tumor cells. We also extended our synergy findings to syngeneic murine sarcoma models, which are poorly susceptible to virus infection. In the absence of robust virus replication, we found trabectedin enhanced viroimmunotherapy efficacy by reducing infiltrating immunosuppressive CD4 T and myeloid cells and stimulating granzyme expression in infiltrating T and natural killer cells to cause immune-mediated tumor regressions. Thus, trabectedin enhances both the direct virus-mediated killing of tumor cells and the viral-induced activation of cytotoxic effector lymphocytes to cause tumor regressions across models. Our data provide a strong rationale for clinical translation as both mechanisms should be simultaneously active in human patients.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"32 4","pages":"200886"},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genetically stable multi-gene edited iPSCs-derived NK cells for enhanced cancer immunotherapy. 遗传稳定的多基因编辑ipscs衍生的NK细胞用于增强癌症免疫治疗。

Molecular therapy. Oncology Pub Date : 2024-09-24 eCollection Date: 2024-12-19 DOI: 10.1016/j.omton.2024.200885

Daekee Kwon, Bo Kyung Moon, Mijung Han, Tae-Wook Lee, Jeehan Lee, Kyung-Sun Kang

{"title":"Genetically stable multi-gene edited iPSCs-derived NK cells for enhanced cancer immunotherapy.","authors":"Daekee Kwon, Bo Kyung Moon, Mijung Han, Tae-Wook Lee, Jeehan Lee, Kyung-Sun Kang","doi":"10.1016/j.omton.2024.200885","DOIUrl":"https://doi.org/10.1016/j.omton.2024.200885","url":null,"abstract":"Chimeric antigen receptor (CAR)-T cell treatment is an innovative drug with excellent therapeutic effects against B cell blood cancer. However, multiple side effects and ultra-high treatment costs must be overcome. Off-the-shelf CAR natural killer (NK) cells can be a good alternative to patient-specific CAR-T cells. The purpose of this study was to combine cellular reprogramming, gene editing, and differentiation technologies to produce full-off-the-shelf NK cells and to verify their efficacy and safety. Genetically stable universal and potent CAR (upCAR)-induced pluripotent stem cells (iPSCs) showed biallelic insertions and deletions in the coding sequence and no off-target effects. upCAR-NK cells showed a very high differentiation yield and in vitro proliferation, and freezing/thawing was possible. In addition, upCAR-NK cells secrete interferon-γ when they meet cancer cells, showing cytotoxic effects in vitro and in vivo. upCAR-NK cells show no obvious toxicity in vivo. In conclusion, this study developed genetically stable upCAR-iPSCs and upCAR-NK cell platform technologies that are less likely to have side effects and can be more economically developed for B cell blood cancer than CAR-T cells. In the future, this technology could be useful in developing a full-off-the-shelf CAR-NK cells anti-cancer immune cell therapy with low side effects, high efficacy, and a low price.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"32 4","pages":"200885"},"PeriodicalIF":0.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CD38 deletion to preserve CAR T cell metabolism and promote functional persistence. 删除 CD38 以保持 CAR T 细胞的新陈代谢并促进功能持久性。

Molecular therapy. Oncology Pub Date : 2024-07-13 eCollection Date: 2024-09-19 DOI: 10.1016/j.omton.2024.200847

Viviana Rubino, Prasad S Adusumilli, Undrakh Ganbaatar

引用次数: 0

Harnessing the power of viroimmunotherapy to overcome challenges in cancer therapy. 利用病毒免疫疗法的力量克服癌症治疗中的挑战。

Molecular therapy. Oncology Pub Date : 2024-05-20 eCollection Date: 2024-06-20 DOI: 10.1016/j.omton.2024.200811

Christopher J LaRocca, Julia Davydova

引用次数: 0

Erratum: Gut microbiota composition is associated with the efficacy of Delta-24-RGDOX in malignant gliomas. 更正：肠道微生物群的组成与 Delta-24-RGDOX 对恶性胶质瘤的疗效有关。

Molecular therapy. Oncology Pub Date : 2024-04-17 eCollection Date: 2024-06-20 DOI: 10.1016/j.omton.2024.200801

Natalie M Meléndez-Vázquez, Teresa T Nguyen, Xuejun Fan, Andrés R López-Rivas, Juan Fueyo, Candelaria Gomez-Manzano, Filipa Godoy-Vitorino

引用次数: 0

Reviving the lost art of meeting reports. 恢复失传的会议报告艺术。

Molecular therapy. Oncology Pub Date : 2024-03-08 eCollection Date: 2024-03-21 DOI: 10.1016/j.omton.2024.200781

Timothy P Cripe

引用次数: 0

Gut microbiota composition is associated with the efficacy of Delta-24-RGDOX in malignant gliomas. 肠道微生物群的组成与 Delta-24-RGDOX 对恶性胶质瘤的疗效有关。

Molecular therapy. Oncology Pub Date : 2024-02-28 eCollection Date: 2024-03-21 DOI: 10.1016/j.omton.2024.200787

Natalie M Meléndez-Vázquez, Teresa T Nguyen, Xuejun Fan, Andrés R López-Rivas, Juan Fueyo, Candelaria Gomez-Manzano, Filipa Godoy-Vitorino

{"title":"Gut microbiota composition is associated with the efficacy of Delta-24-RGDOX in malignant gliomas.","authors":"Natalie M Meléndez-Vázquez, Teresa T Nguyen, Xuejun Fan, Andrés R López-Rivas, Juan Fueyo, Candelaria Gomez-Manzano, Filipa Godoy-Vitorino","doi":"10.1016/j.omton.2024.200787","DOIUrl":"https://doi.org/10.1016/j.omton.2024.200787","url":null,"abstract":"Glioblastoma, the most common primary brain tumor, has a 6.8% survival rate 5 years post diagnosis. Our team developed an oncolytic adenovirus with an OX-40L expression cassette named Delta-24-RGDOX. While studies have revealed the interaction between the gut microbiota and immunotherapy agents, there are no studies linking the gut microbiota with viroimmunotherapy efficacy. We hypothesize that gut bacterial signatures will be associated with oncolytic viral therapy efficacy. To test this hypothesis, we evaluated the changes in gut microbiota in two mouse cohorts: (1) GSC-005 glioblastoma-bearing mice treated orally with indoximod, an immunotherapeutic agent, or with Delta-24-RGDOX by intratumoral injection and (2) a mouse cohort harboring GL261-5 tumors used to mechanistically evaluate the importance of CD4+ T cells in relation to viroimmunotherapy efficacy. Microbiota assessment indicated significant differences in the structure of the gut bacterial communities in viroimmunotherapy-treated animals with higher survival compared with control or indoximod-treated animals. Moreover, viroimmunotherapy-treated mice with prolonged survival had a higher abundance of Bifidobacterium. The CD4+ T cell depletion was associated with gut dysbiosis, lower mouse survival, and lower antitumor efficacy of the therapy. These findings suggest that microbiota modulation along the gut-glioma axis contributes to the clinical efficacy and patient survival of viroimmunotherapy treated animals.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"32 1","pages":"200787"},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0