Molecular therapy. Oncology最新文献_第2页

Regulation of the brain tumor microenvironment by focused ultrasound. 聚焦超声对脑肿瘤微环境的调控。

Molecular therapy. Oncology Pub Date : 2025-05-14 eCollection Date: 2025-06-18 DOI: 10.1016/j.omton.2025.200994

Kang Fu, Huijing Hu, Xiaodong Zhou, Le Li, Li Yan

{"title":"Regulation of the brain tumor microenvironment by focused ultrasound.","authors":"Kang Fu, Huijing Hu, Xiaodong Zhou, Le Li, Li Yan","doi":"10.1016/j.omton.2025.200994","DOIUrl":"10.1016/j.omton.2025.200994","url":null,"abstract":"Glioblastoma and other high-grade primary malignant brain tumors are a serious threat to the life and health of patients; consequently, their accurate diagnosis and treatment are crucial. Brain tumors are usually treated by surgical resection, radiotherapy and drug chemotherapy; however, such treatments have side effects such as trauma, infection, and radiation exposure. Furthermore, owing to limitations in conditions such as the skull and blood-brain barrier, noninvasive treatment and diagnosis of brain tumors have been challenging. In recent years, focused ultrasound (FUS) technology has shown great advantages and application potential because of its noninvasive and energy-focusing characteristics in brain tumors. From the perspective of the brain tumor microenvironment, FUS can produce mechanical and thermal effects by delivering sound waves to brain tissue; these sound waves can induce blood-brain barrier opening, radiation sensitization, targeted substance delivery, immune enhancement, angiogenesis and destruction, oxidative stress, interstitial hydraulic regulation, and brain tumor marker sonobiopsy. The feasibility and safety data from both animal models and clinical trials support FUS as having great potential for use in the diagnosis and treatment of brain tumors.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"33 2","pages":"200994"},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304307","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

Targeted expansion of cytotoxic T cells using IL-12 and CD137L supplementation enhances antitumor efficacy. 利用IL-12和CD137L补充靶向扩增细胞毒性T细胞可增强抗肿瘤效果。

Molecular therapy. Oncology Pub Date : 2025-05-14 eCollection Date: 2025-06-18 DOI: 10.1016/j.omton.2025.200996

Marta Sanz, Brendan T Mann, Elyse K McMahon, Alberto Bosque, Samuel Simmens, Natalia Soriano-Sarabia

{"title":"Targeted expansion of cytotoxic T cells using IL-12 and CD137L supplementation enhances antitumor efficacy.","authors":"Marta Sanz, Brendan T Mann, Elyse K McMahon, Alberto Bosque, Samuel Simmens, Natalia Soriano-Sarabia","doi":"10.1016/j.omton.2025.200996","DOIUrl":"10.1016/j.omton.2025.200996","url":null,"abstract":"The increasing success of allogenic Vδ2 T cell immunotherapy for the treatment of cancer has been demonstrated in recent studies. Vδ2 T cells recognize phosphoantigens, intermediates of the mevalonate pathway, through butyrophilin molecules, and they are not major histocompatibility complex (MHC) restricted. Allogeneic transfer of in vitro expanded Vδ2 T cells has shown more promising results than autologous strategies, although the clinical benefit remains limited. One of the issues leading to less-than-optimal responses relates to the polyclonal expansion of Vδ2 T cell subsets with variable cytotoxic capacity. Previous work developed protocols to expand Vδ2 T cells, although to our knowledge, ours is the first comprehensive study that has produced a simple, antigen-presenting feeder-free culture that produced an average expansion of 3,000-fold and more than 95% pure Vδ2 T cells avoiding additional isolation steps. Here, we show the in vitro expansion of cytotoxic Vδ2 T cells expressing CD16 and NKG2A enriched in granzyme B that displayed enhanced antitumor activity of up to 40% against leukemia and ovarian, breast, and lung cancer cells. Our work warrants clinical testing to evaluate the therapeutic potential of these highly cytotoxic cells, paving the way for improved efficacy of personalized cell-based immunotherapies.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"33 2","pages":"200996"},"PeriodicalIF":0.0,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304308","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

K12-ligand-based CAR T cell therapy for CD7-positive T cell malignancies. 基于k12配体的CAR - T细胞治疗cd7阳性T细胞恶性肿瘤。

Molecular therapy. Oncology Pub Date : 2025-04-29 eCollection Date: 2025-06-18 DOI: 10.1016/j.omton.2025.200988

Nienke Visser, Macarena González-Corrales, Jimena Álvarez-Freile, Maurien G Pruis, Lena Rockstein, Harm Jan Lourens, Jan Jacob Schuringa, Tom van Meerten, Gerwin Huls, Edwin Bremer

{"title":"K12-ligand-based CAR T cell therapy for CD7-positive T cell malignancies.","authors":"Nienke Visser, Macarena González-Corrales, Jimena Álvarez-Freile, Maurien G Pruis, Lena Rockstein, Harm Jan Lourens, Jan Jacob Schuringa, Tom van Meerten, Gerwin Huls, Edwin Bremer","doi":"10.1016/j.omton.2025.200988","DOIUrl":"10.1016/j.omton.2025.200988","url":null,"abstract":"Chimeric antigen receptor (CAR)-based therapy is of interest for relapsed or refractory (r/r) T cell acute lymphoblastic leukemia (T-ALL) and T cell lymphomas. A prominent target antigen for this is the receptor CD7, which is expressed in ∼95% of T-ALL, ∼50% of peripheral T cell lymphomas, as well as 10% of acute myeloid leukemias. Here, we preclinically evaluated and compared CD7-targeted ligand K12-based CAR-T to an scFvCD7-based CAR-T construct. K12 CAR-T cells produced significantly higher interferon gamma (IFN-γ) after CD7 activation compared to scFv-CD7 CAR-T cells. Similarly, in a JurkatNFAT-luc reporter cell line expressing the respective CAR, CD7-induced luminescence was significantly higher by the K12 CAR than the scFv-CD7 CAR. K12 CAR-T treatment selectively and specifically eliminated a panel of CD7-positive, but not CD7-negative, cell lines and eliminated acute-T-cell-leukemia-patient-derived and acute myeloid leukemia blasts in an effector-to-target ratio-dependent manner. Further, K12 CAR-T cells had prominent anti-leukemic activity in an intravenously (i.v.) injected Jurkat leukemia mouse model, with no detectable disease in three out of five mice treated with K12 CAR-T. Therefore, K12 CAR T cell therapy might be of use for the treatment of r/r patients with CD7-positive T cell leukemia/lymphoma and acute myeloid leukemia (AML).","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"33 2","pages":"200988"},"PeriodicalIF":0.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532551","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

Boosting anti-tumor immunity with TILT-517 oncolytic adenovirus and checkpoint blockade in renal cell carcinoma. TILT-517溶瘤腺病毒增强肾细胞癌的抗肿瘤免疫和检查点阻断。

Molecular therapy. Oncology Pub Date : 2025-04-03 eCollection Date: 2025-06-18 DOI: 10.1016/j.omton.2025.200979

Victor Arias, Tatiana V Kudling, James H A Clubb, Elise Jirovec, Santeri A Pakola, Mirte Van der Heijden, Saru Basnet, Dafne C A Quixabeira, Lyna Haybout, Nea Ojala, Susanna Grönberg-Vähä-Koskela, Anna Kanerva, Antti Rannikko, João M Santos, Victor Cervera-Carrascon, Otto Hemminki, Akseli Hemminki

{"title":"Boosting anti-tumor immunity with TILT-517 oncolytic adenovirus and checkpoint blockade in renal cell carcinoma.","authors":"Victor Arias, Tatiana V Kudling, James H A Clubb, Elise Jirovec, Santeri A Pakola, Mirte Van der Heijden, Saru Basnet, Dafne C A Quixabeira, Lyna Haybout, Nea Ojala, Susanna Grönberg-Vähä-Koskela, Anna Kanerva, Antti Rannikko, João M Santos, Victor Cervera-Carrascon, Otto Hemminki, Akseli Hemminki","doi":"10.1016/j.omton.2025.200979","DOIUrl":"10.1016/j.omton.2025.200979","url":null,"abstract":"Elevated levels of immune infiltration found in renal cell carcinoma are often associated with poor patient prognosis, likely due to T cell exhaustion and an immunosuppressive tumor microenvironment, which limits the efficacy of current immunotherapies. In this study, we focused on the use of Ad5/3-E2F-d24-hIL7 (TILT-517), an oncolytic adenovirus expressing interleukin-7, as a strategy to selectively lyse tumors. This approach also seeks to activate infiltrating immune cells, thereby reprogramming the immune landscape characteristic of renal cell carcinoma tumors. Furthermore, we evaluated the combination of TILT-517 with immune checkpoint inhibitors, main immunotherapeutic component for this disease. Anti-tumor efficacy was significantly observed in ex vivo patient-derived tumors when treated with TILT-517 in monotherapy and in treatment combination. Cellular and proteomic changes were detected in the tumor microenvironment, including enhanced cytotoxicity of effector populations such as CD4+, CD8+ T cells, natural killer, and natural killer T cells. In vivo, we developed a novel syngeneic Syrian hamster model for renal cancer, and TILT-517+anti-PD-L1 group presented significant enhanced tumor growth control and led to an increased number of effector and antigen-presenting cells compared to anti-PD-L1 monotherapy. Hence, TILT-517 offers a promising approach for renal cell carcinoma treatment, boosting therapeutic efficacy and reshaping the tumor microenvironment.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"33 2","pages":"200979"},"PeriodicalIF":0.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532550","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

What a model: A newly developed pancreatic murine cell line permissive to adenoviral replication. 什么是模型：一种允许腺病毒复制的新开发的胰腺小鼠细胞系。

Molecular therapy. Oncology Pub Date : 2025-03-13 eCollection Date: 2025-03-20 DOI: 10.1016/j.omton.2025.200956

Manlio Fusciello, Vincenzo Cerullo

引用次数: 0

Enhancing ovarian cancer treatment by synergistically targeting HER2 and PD-L1. 协同靶向HER2和PD-L1增强卵巢癌治疗。

Molecular therapy. Oncology Pub Date : 2025-03-11 eCollection Date: 2025-03-20 DOI: 10.1016/j.omton.2025.200960

Shuo Zhang, Qi Pan, Kangchun Wang

引用次数: 0

Cracking the code for more effective treatments for hepatocellular carcinomas: Promise and a path for immunovirotherapy. 破解更有效治疗肝细胞癌的密码：免疫病毒治疗的前景和途径。

Molecular therapy. Oncology Pub Date : 2025-03-10 eCollection Date: 2025-03-20 DOI: 10.1016/j.omton.2025.200955

Emil Lou

引用次数: 0

Mitigating IL-12-induced toxicities: A path forward with TNF inhibition. 缓解il -12诱导的毒性：TNF抑制的途径

Molecular therapy. Oncology Pub Date : 2025-03-04 eCollection Date: 2025-03-20 DOI: 10.1016/j.omton.2025.200951

Julia Davydova, Christopher J LaRocca

引用次数: 0

Mission impossible: mesenchymal stem cells delivering oncolytic viruses before self-destruction. 不可能完成的任务：间充质干细胞在自我毁灭前传递溶瘤病毒。

Molecular therapy. Oncology Pub Date : 2025-02-28 eCollection Date: 2025-03-20 DOI: 10.1016/j.omton.2025.200943

Jia-Xu Li, Janica C Wong

引用次数: 0

The 16th International Oncolytic Virus Conference: Advancing oncolytic virotherapy by balancing anti-tumor and anti-viral immunity. 第16届国际溶瘤病毒会议：通过平衡抗肿瘤和抗病毒免疫来推进溶瘤病毒治疗。

Molecular therapy. Oncology Pub Date : 2025-02-28 eCollection Date: 2025-03-20 DOI: 10.1016/j.omton.2025.200950

Eftychia Stavrakaki, Anne Everts, Bernadette G van den Hoogen, Martine L M Lamfers

引用次数: 0