Molecular therapy. Oncology最新文献

Engineered retargeting to overcome systemic delivery challenges in oncolytic adenoviral therapy. 工程重靶向以克服溶瘤腺病毒治疗中的全身递送挑战。

Molecular therapy. Oncology Pub Date : 2025-06-06 eCollection Date: 2025-06-18 DOI: 10.1016/j.omton.2025.201005

Louise Leparc, Hiroaki Wakimoto

引用次数: 0

Novel synthetic peptide-based vaccine shows promise against prostate cancer. 一种新的合成肽疫苗显示出对抗前列腺癌的希望。

Molecular therapy. Oncology Pub Date : 2025-06-04 eCollection Date: 2025-06-18 DOI: 10.1016/j.omton.2025.201000

Karina Vázquez-Arreguín

引用次数: 0

Novel immunotherapy for multiple myeloma involving activation of plasmacytoid dendritic cells. 涉及浆细胞样树突状细胞活化的多发性骨髓瘤新免疫疗法。

Molecular therapy. Oncology Pub Date : 2025-06-04 eCollection Date: 2025-06-18 DOI: 10.1016/j.omton.2025.201004

Masayuki Kurimoto, Tomohiro Watanabe, Masatoshi Kudo

引用次数: 0

The safer effector cell? Potential of CD147 CAR NK cells to tackle tumors with lower toxicity. 更安全的效应细胞？CD147 CAR - NK细胞治疗低毒性肿瘤的潜力。

Molecular therapy. Oncology Pub Date : 2025-06-04 eCollection Date: 2025-06-18 DOI: 10.1016/j.omton.2025.200998

Alan Hodges, Shu-Hsia Chen, Ping-Ying Pan

引用次数: 0

Oncolytic adeno-immunotherapy improves allogeneic adoptive HER2.CAR-NK function against pancreatic ductal adenocarcinoma. 溶瘤腺免疫疗法改善同种异体过继性HER2。CAR-NK对胰管腺癌的作用。

Molecular therapy. Oncology Pub Date : 2025-05-26 eCollection Date: 2025-06-18 DOI: 10.1016/j.omton.2025.201006

Greyson Biegert, Amanda Rosewell Shaw, Daisuke Morita, Caroline Porter, Ryu Matsumoto, Lisa Jatta, Noah Crooks, Mae Woods, Qizhi Cathy Yao, Robin Parihar, Masataka Suzuki

{"title":"Oncolytic adeno-immunotherapy improves allogeneic adoptive HER2.CAR-NK function against pancreatic ductal adenocarcinoma.","authors":"Greyson Biegert, Amanda Rosewell Shaw, Daisuke Morita, Caroline Porter, Ryu Matsumoto, Lisa Jatta, Noah Crooks, Mae Woods, Qizhi Cathy Yao, Robin Parihar, Masataka Suzuki","doi":"10.1016/j.omton.2025.201006","DOIUrl":"10.1016/j.omton.2025.201006","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) responds poorly to conventional treatments and immunotherapy. We previously developed a binary oncolytic/helper-dependent adenovirus system (CAdTrio) that facilitated oncolysis and expressed the immunomodulatory molecule interleukin-12 and a programmed death ligand 1 (PD-L1) blocking mini-antibody. Given that CAdTrio enhanced endogenous natural killer (NK) cell anti-tumor activity in humanized mice bearing PDAC tumors and that NK cells can be adoptively transferred to patients safely in the allogeneic setting, we hypothesized that a combination of CAdTrio and allogeneic NK cells expressing a HER2-specific chimeric antigen receptor (HER2.CAR-NK) would be an effective, entirely \"off-the-shelf\" treatment against PDAC. We found that CAdTrio-derived immunomodulatory molecules prolonged HER2.CAR-NK persistence at tumor sites, allowing long-term tumor growth control and improved survival in both humanized mice and a heterogeneous PDAC patient-derived xenografts (PDX) model. This effect was based on CAdTrio-derived transgene support that shifted HER2.CAR-NK gene expression to that resembling an NK memory-like phenotype. Additionally, this allogeneic combination therapy was tolerated in humanized mice. Together, these data suggest that CAdTrio and HER2.CAR-NK cell combination immunotherapy may be a novel and effective option for the treatment for immunologically \"cold\" PDAC tumors.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"33 2","pages":"201006"},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370036","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

Emerging roles of protein arginine methyltransferase in multiple myeloma. 蛋白精氨酸甲基转移酶在多发性骨髓瘤中的新作用。

Molecular therapy. Oncology Pub Date : 2025-05-26 eCollection Date: 2025-06-18 DOI: 10.1016/j.omton.2025.201003

Sajida Fady Qaddoura, Enze Liu, Brian A Walker, Ngoc Tung Tran

{"title":"Emerging roles of protein arginine methyltransferase in multiple myeloma.","authors":"Sajida Fady Qaddoura, Enze Liu, Brian A Walker, Ngoc Tung Tran","doi":"10.1016/j.omton.2025.201003","DOIUrl":"10.1016/j.omton.2025.201003","url":null,"abstract":"Multiple myeloma (MM) is a cancer of plasma cells characterized by the clonal expansion of abnormal plasma cells in the bone marrow. These malignant cells overcrowd the bone marrow, disrupt normal hematopoiesis, and produce excessive amounts of immunoglobulins, leading to severe clinical manifestations. Despite significant advancements in treatment, relapsed/refractory MM remains incurable. Protein arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is a critical post-translational modification involved in regulating various cellular processes. Aberrant expression of PRMTs has been strongly linked to poor prognosis in many cancers, including MM. Among the PRMT family, PRMT1, PRMT4 (CARM1), and PRMT5 have emerged as potential therapeutic targets for MM. This review will first explore the expression patterns of PRMTs in MM and assess their association with disease prognosis. We will then provide a comprehensive overview of the functions of these PRMTs in MM pathology, discuss the development of PRMT inhibitors currently being evaluated in clinical trials, and offer insights into the potential of targeting PRMTs for MM treatment in clinical settings.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"33 2","pages":"201003"},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311154","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

Tumor-specific AAV delivery of interleukin-12 enhances antitumor immunity and safety in ovarian cancer xenograft mouse model. 肿瘤特异性AAV传递白介素-12增强卵巢癌异种移植小鼠模型的抗肿瘤免疫和安全性。

Molecular therapy. Oncology Pub Date : 2025-05-24 eCollection Date: 2025-06-18 DOI: 10.1016/j.omton.2025.201002

Chuyuan Chen, Yongji Jiang, Chuan Feng, Qingyun Zhou, Xingrong Luo, Lili Cai, Lei Zhao

{"title":"Tumor-specific AAV delivery of interleukin-12 enhances antitumor immunity and safety in ovarian cancer xenograft mouse model.","authors":"Chuyuan Chen, Yongji Jiang, Chuan Feng, Qingyun Zhou, Xingrong Luo, Lili Cai, Lei Zhao","doi":"10.1016/j.omton.2025.201002","DOIUrl":"10.1016/j.omton.2025.201002","url":null,"abstract":"Interleukin-12 (IL-12) is a promising pro-inflammatory cytokine for cancer immunotherapy, but its toxicity and short half-life in serum limit its clinical application. Tumor-targeted delivery of IL-12 by fusion with either antibody or secretion by chimeric antigen receptor T (CAR-T) cells showed reduced systematic toxicity; however, the poor tumor microenvironment (TME) response or the lack of systematic IL-12 regulation still remains risk of low efficacy or high toxicity. Here, we developed TME-specific delivery of IL-12 by a tumor-targeted adeno-associated virus 9 (tAAV9). The tAAV9 was formed by an anti-folate receptor 1 (anti-FOLR1) antibody fragment conjugated with AAV9 via highly efficient Spy-ligation. With targeted infection of FOLR1+ cells in vivo, intravenous (i.v.) administration of tAAV9 specifically delivered IL-12 (tAAV9-IL-12) to TME and significantly suppressed tumor progression with favorable safety profile compared with rAAV9 (recombinant wild-type AAV9) delivery. Moreover, the IL-12 level in the serum was decreased significantly with the suppression of tAAV9-IL-12-infected tumor cell, so that generates promising negative feedback to ensure the safety profile.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"33 2","pages":"201002"},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319148","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

Quantitative and qualitative metrics of tumor stroma in predicting ovarian cancer outcomes and expansion of its study with AI-based tools. 肿瘤基质在预测卵巢癌预后中的定量和定性指标及其基于人工智能工具的研究扩展。

Molecular therapy. Oncology Pub Date : 2025-05-24 eCollection Date: 2025-06-18 DOI: 10.1016/j.omton.2025.201001

Morgann Madill, Arpit Aggarwal, Anant Madabhushi, Britt K Erickson, Andrew C Nelson, Emil Lou, Martina Bazzaro

{"title":"Quantitative and qualitative metrics of tumor stroma in predicting ovarian cancer outcomes and expansion of its study with AI-based tools.","authors":"Morgann Madill, Arpit Aggarwal, Anant Madabhushi, Britt K Erickson, Andrew C Nelson, Emil Lou, Martina Bazzaro","doi":"10.1016/j.omton.2025.201001","DOIUrl":"10.1016/j.omton.2025.201001","url":null,"abstract":"Epithelial ovarian cancer remains one of the deadliest gynecologic malignancies, with late-stage diagnosis, high recurrence rates, and resistance to platinum-based chemotherapy contributing to poor survival outcomes. Central to the effective management of ovarian cancer is the thorough evaluation of diagnostic and prognostic indicators. Critical determinants encompass the extent of the tumor; its stage and grade; and level of the circulating biomarker, CA-125. Additional tumor cell-centric factors such as BRCA1/2 mutation status, homologous recombination deficiency, and folate receptor-alpha (FRα) protein levels inform initial treatment and maintenance strategies. Unfortunately, these markers alone cannot fully predict outcomes or significantly improve survival rates. This review emphasizes the body of data suggesting that both quantitative and qualitative metrics of tumor stroma play a crucial role in the prognosis and outcomes of epithelial ovarian cancer. We examine quantitative and qualitative metrics such as stromal proportion, tumor density, stiffness, and texture. We explore how artificial intelligence (AI) tools advance the measurement of these parameters, offering unprecedented opportunities to integrate stromal biomarkers into clinical decision-making. By synthesizing emerging evidence, we propose a framework for leveraging stromal properties-individually and in combination-as novel prognostic indicators to improve outcomes for patients with ovarian cancer.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"33 2","pages":"201001"},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311157","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

Real-time imaging reveals radiation-induced intratumor apoptosis via nutrient and oxygen deprivation following vascular damage. 实时成像显示血管损伤后通过营养和氧气剥夺引起的辐射诱导的肿瘤内凋亡。

Molecular therapy. Oncology Pub Date : 2025-05-20 eCollection Date: 2025-06-18 DOI: 10.1016/j.omton.2025.200997

Go Kagiya, Ryohei Ogawa, Toshihide Matsumoto, Fuminori Hyodo, Nanako Abe, Ami Yuzawa, Haru Takeuchi, Miki Aoyagi, Ayaka Sato, Kei Yamashita, Masanori Hatashita

{"title":"Real-time imaging reveals radiation-induced intratumor apoptosis via nutrient and oxygen deprivation following vascular damage.","authors":"Go Kagiya, Ryohei Ogawa, Toshihide Matsumoto, Fuminori Hyodo, Nanako Abe, Ami Yuzawa, Haru Takeuchi, Miki Aoyagi, Ayaka Sato, Kei Yamashita, Masanori Hatashita","doi":"10.1016/j.omton.2025.200997","DOIUrl":"10.1016/j.omton.2025.200997","url":null,"abstract":"Radiotherapy exerts significant effects on the tumor microenvironment. Radiation is known to induce direct tumor cell death through intrinsic factors (e.g., DNA repair activity and p53-mediated radiation sensitivity). It also induces indirect cell death by altering the tumor microenvironment. However, current knowledge is based on indirect evidence. We focused on apoptosis, a form of cell death, to elucidate the mechanisms underlying radiation-induced apoptosis in tumors. Using apoptosis-imaging cells and real-time imaging technology, we investigated the pathways involved in radiation-induced apoptosis in the tumor environment and found that the mechanism triggering early apoptosis following X-ray exposure involves minimal participation of the immune system. Furthermore, we demonstrated that apoptosis in tumors is an indirect form of cell death as well, primarily driven by radiation-induced damage to the tumor vasculature, which leads to reduced blood flow, resulting in nutrient and oxygen deprivation within cancerous tissue, which induces apoptosis. The presence of nutrient deprivation and hypoxia, mediated by tumor vascular damage, suggests the possibility of inducing not only apoptosis but also other forms of cell death (e.g., autophagic cell death and necrosis-like cell death) based on these mechanisms. These pathways provide valuable insights for the development of more effective radiotherapy strategies.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"33 2","pages":"200997"},"PeriodicalIF":0.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304306","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

Identification of dynamic network biomarker ITGB1 for erlotinib pre-resistance using single-cell differential covariance entropy. 利用单细胞微分协方差熵鉴定厄洛替尼预耐药动态网络生物标志物ITGB1。

Molecular therapy. Oncology Pub Date : 2025-05-15 eCollection Date: 2025-06-18 DOI: 10.1016/j.omton.2025.200993

Xuerong Gu, Qiwen Huang, Yucheng Huang, Dandan Ding, Jiayuan Zhong, Shengming Lin, Yingxin Yu, Hui Wang, Chang Liu, Pei Chen, Chunbo Chen, Wei Luo, Haiyu Zhou, Rui Liu, Fei Ling

{"title":"Identification of dynamic network biomarker ITGB1 for erlotinib pre-resistance using single-cell differential covariance entropy.","authors":"Xuerong Gu, Qiwen Huang, Yucheng Huang, Dandan Ding, Jiayuan Zhong, Shengming Lin, Yingxin Yu, Hui Wang, Chang Liu, Pei Chen, Chunbo Chen, Wei Luo, Haiyu Zhou, Rui Liu, Fei Ling","doi":"10.1016/j.omton.2025.200993","DOIUrl":"10.1016/j.omton.2025.200993","url":null,"abstract":"Acquired erlotinib resistance is the primary cause of treatment failure in patients with non-small cell lung cancer (NSCLC). Most current research focuses on end-stage resistance, whereas early events leading to resistance have been largely overlooked. In this study, we developed a novel dynamic network biomarker (DNB) method called single-cell differential covariance entropy (scDCE) to identify the pre-resistance state and associated DNB genes. We identified the DNB core gene ITGB1 using protein-protein interactions (PPIs) and Mendelian randomization (MR) analyses. Cell Counting Kit-8 assay demonstrated that ITGB1 downregulation increases the sensitivity of PC9 cells to erlotinib. Survival analyses suggested that high ITGB1 expression was associated with poor prognosis in NSCLC. Mechanistically, we found that ITGB1 and DNB-neighboring genes were significantly enriched in the focal adhesion pathway, where ITGB1 upregulates the expression of PTK2 (focal adhesion kinase), leading to phosphorylation of downstream effectors, which activated the PI3K-Akt and MAPK signaling pathways to promote cell proliferation and mediate erlotinib resistance. Additionally, the transcription factor MAX/MNT binds to the ITGB1 promoter, synergistically regulating its expression. The experiment also shows that the erlotinib-trametinib combination therapy effectively inhibits resistance. These findings provide new clues for future research on erlotinib resistance mechanisms and early intervention.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"33 2","pages":"200993"},"PeriodicalIF":0.0,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370035","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