Molecular therapy. Oncology最新文献_第4页

Retraction Notice to: MYB Proto-oncogene-like 1-TWIST1 Axis Promotes Growth and Metastasis of Hepatocellular Carcinoma Cells. 撤回通知：MYB原癌基因样1-TWIST1轴促进肝癌细胞生长和转移。

Molecular therapy. Oncology Pub Date : 2024-12-13 eCollection Date: 2024-12-19 DOI: 10.1016/j.omton.2024.200918

Binhui Xie, Yao Liu, Zhenxian Zhao, Qingquan Liu, Xiaonong Wang, Yuankang Xie, Yanhong Liu, Yuwen Liu, Yan Yang, Jianting Long, Qiangsheng Dai, Heping Li

引用次数: 0

Thank you to our 2024 reviewers. 感谢我们的2024位评审。

Molecular therapy. Oncology Pub Date : 2024-12-06 eCollection Date: 2024-12-19 DOI: 10.1016/j.omton.2024.200912

引用次数: 0

SAP30, a novel autophagy regulatory gene in neuroblastoma. 神经母细胞瘤中的新型自噬调控基因 SAP30

Molecular therapy. Oncology Pub Date : 2024-12-06 eCollection Date: 2025-03-20 DOI: 10.1016/j.omton.2024.200916

Anup S Pathania, Anjana Murugan, Areem Zahid, Haritha Chava, Don W Coulter, George A Calin, Kishore B Challagundla

{"title":"SAP30, a novel autophagy regulatory gene in neuroblastoma.","authors":"Anup S Pathania, Anjana Murugan, Areem Zahid, Haritha Chava, Don W Coulter, George A Calin, Kishore B Challagundla","doi":"10.1016/j.omton.2024.200916","DOIUrl":"10.1016/j.omton.2024.200916","url":null,"abstract":"Neuroblastoma (NB), a devastating pediatric cancer originating from neural crest cells crucial for nervous system development, poses a significant therapeutic challenge. Despite chemotherapy being the primary treatment, approximately 70% of high-risk NB cases develop resistance. Autophagy is vital for neuronal development, balance, and differentiation of neural stem cells into mature neurons. However, the intricate mechanisms governing autophagy and the pivotal genes orchestrating its regulation in NB remain largely elusive. In this study, we first identified Sin3A Associated Protein 30 (SAP30) as a novel regulator of autophagy in NB. Silencing SAP30 inhibits autophagy and disrupts starvation-induced physiological autophagy in NB cells. Conversely, ectopic expression of SAP30 induces autophagy in NB cells under normal or starvation conditions. Mechanistically, SAP30 transcriptionally regulates STX17, a crucial protein involved in autophagosome-lysosome fusion during autophagy. Reduction of SAP30 decreases STX17 expression, hindering its translocation to the autophagic membrane and inhibiting autophagosome-lysosome fusion. SAP30-mediated autophagy enhances cell growth and provides protection in NB cells treated with chemotherapy drugs. Notably, suppressing SAP30 in vivo increases LC3B accumulation, an autophagy marker, along with reduced proliferation markers, both in vivo and in PDX tumors. Therefore, SAP30 emerges as a potential target to enhance NB responsiveness to chemotherapy drugs.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"33 1","pages":"200916"},"PeriodicalIF":0.0,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797277","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

Enhancing immune response and survival in hepatocellular carcinoma with novel oncolytic Jurona virus and immune checkpoint blockade. 新型溶瘤性Jurona病毒和免疫检查点阻断增强肝细胞癌的免疫应答和生存。

Molecular therapy. Oncology Pub Date : 2024-11-26 eCollection Date: 2024-12-19 DOI: 10.1016/j.omton.2024.200913

Mulu Z Tesfay, Yuguo Zhang, Khandoker U Ferdous, Mika A Taylor, Aleksandra Cios, Randal S Shelton, Camila C Simoes, Chelsae R Watters, Oumar Barro, Natalie M Elliott, Bahaa Mustafa, Jean Christopher Chamcheu, Alicia L Graham, Charity L Washam, Duah Alkam, Allen Gies, Stephanie D Byrum, Emmanouil Giorgakis, Steven R Post, Thomas Kelly, Jun Ying, Omeed Moaven, Chiswili Y Chabu, Martin E Fernandez-Zapico, Dan G Duda, Lewis R Roberts, Rang Govindarajan, Mitesh J Borad, Martin J Cannon, Alexei G Basnakian, Bolni M Nagalo

{"title":"Enhancing immune response and survival in hepatocellular carcinoma with novel oncolytic Jurona virus and immune checkpoint blockade.","authors":"Mulu Z Tesfay, Yuguo Zhang, Khandoker U Ferdous, Mika A Taylor, Aleksandra Cios, Randal S Shelton, Camila C Simoes, Chelsae R Watters, Oumar Barro, Natalie M Elliott, Bahaa Mustafa, Jean Christopher Chamcheu, Alicia L Graham, Charity L Washam, Duah Alkam, Allen Gies, Stephanie D Byrum, Emmanouil Giorgakis, Steven R Post, Thomas Kelly, Jun Ying, Omeed Moaven, Chiswili Y Chabu, Martin E Fernandez-Zapico, Dan G Duda, Lewis R Roberts, Rang Govindarajan, Mitesh J Borad, Martin J Cannon, Alexei G Basnakian, Bolni M Nagalo","doi":"10.1016/j.omton.2024.200913","DOIUrl":"https://doi.org/10.1016/j.omton.2024.200913","url":null,"abstract":"Members of the Vesiculovirus genus including Jurona virus (JURV) have emerged as promising immunotherapeutic agents, characterized by their tumor selectivity, fast kinetics, low seroprevalence, and minimal toxicity in humans. Here, we demonstrate that the administration of JURV leads to tumor regression in both hepatocellular carcinoma (HCC) xenograft and syngeneic models. Furthermore, our findings indicate that combining JURV and anti-PD-1 therapy reduced tumor burden and improved survival rates over JURV or anti-PD-1 alone in an orthotopic HCC model. Proteogenomic analysis of JURV-treated, murine HCC tumors demonstrates that the therapeutic effects of the combination of JURV and anti-PD-1 are predominantly driven by coordinated activation of immune effectors, which modulate the tumor microenvironment into a state conducive to anti-tumor activity. Our results establish JURV as a potent candidate for immunovirotherapy in HCC, capable of modulating immune response and synergizing with standard of care for HCC to prolong survival in preclinical models. Further, this research deepens our understanding of JURV's anti-tumoral mechanisms and highlights its potential as a novel approach to HCC treatment strategies.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"32 4","pages":"200913"},"PeriodicalIF":0.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934400","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

Employing splice-switching oligonucleotides and AAVrh74.U7 snRNA to target insulin receptor splicing and cancer hallmarks in osteosarcoma. 采用剪接开关寡核苷酸和AAVrh74。U7 snRNA靶向骨肉瘤中的胰岛素受体剪接和癌症特征。

Molecular therapy. Oncology Pub Date : 2024-11-23 eCollection Date: 2024-12-19 DOI: 10.1016/j.omton.2024.200908

Safiya Khurshid, Akila S Venkataramany, Matias Montes, John F Kipp, Ryan D Roberts, Nicolas Wein, Frank Rigo, Pin-Yi Wang, Timothy P Cripe, Dawn S Chandler

{"title":"Employing splice-switching oligonucleotides and AAVrh74.U7 snRNA to target insulin receptor splicing and cancer hallmarks in osteosarcoma.","authors":"Safiya Khurshid, Akila S Venkataramany, Matias Montes, John F Kipp, Ryan D Roberts, Nicolas Wein, Frank Rigo, Pin-Yi Wang, Timothy P Cripe, Dawn S Chandler","doi":"10.1016/j.omton.2024.200908","DOIUrl":"10.1016/j.omton.2024.200908","url":null,"abstract":"Patients with osteosarcoma (OS), a debilitating pediatric bone malignancy, have limited treatment options to combat aggressive disease. OS thrives on insulin growth factor (IGF)-mediated signaling that can facilitate cell proliferation. Previous efforts to target IGF-1R signaling were mostly unsuccessful, likely due to compensatory signaling through alternative splicing of the insulin receptor (IR) to the proliferative IR-A isoform. Here, we leverage splice-switching oligonucleotides (SSOs) to mitigate IR splicing toward the IR-B isoform. We show that SSOs can modulate cancer cell hallmarks and anoikis-resistant growth. Furthermore, we engineered the SSO sequence in an U7 snRNA packaged in an adeno-associated virus (AAV) to test the feasibility of viral vector-mediated gene therapy delivery. We noted modest increases in IR-B isoform levels after virus transduction, which prompted us to investigate the role of combinatorial treatments with dalotuzumab, an anti-IGF-1R monoclonal antibody. After observing additive impacts on phosphoprotein phosphorylation and anoikis-resistant growth with the dalotuzumab and SSO combination, we treated OS cells with dalotuzumab and the AAVrh74.U7 snRNA IR virus, which significantly slowed OS cell proliferation. While these viruses require further optimization, we highlight the potential for SSO therapy and viral vector delivery, as it may offer new treatment avenues for OS patients and be translated to other cancers.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"32 4","pages":"200908"},"PeriodicalIF":0.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886632","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

Clinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic target. 循环剪接因子在前列腺癌中的临床价值：SRRM1作为一种新的预测生物标志物和治疗靶点

Molecular therapy. Oncology Pub Date : 2024-11-23 eCollection Date: 2024-12-19 DOI: 10.1016/j.omton.2024.200910

Antonio J Montero-Hidalgo, Enrique Gómez-Gómez, Manuel Galán-Cañete, Francisco Porcel-Pastrana, Jesús M Pérez-Gómez, María Ortega-Bellido, Julia Carrasco-Valiente, Laura Chamorro-Castillo, Juan P Campos-Hernández, Oriol A Rangel-Zuñiga, Teresa González-Serrano, Rafael Sánchez-Sánchez, André Sarmento-Cabral, Manuel D Gahete, Juan M Jiménez-Vacas, Raúl M Luque

{"title":"Clinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic target.","authors":"Antonio J Montero-Hidalgo, Enrique Gómez-Gómez, Manuel Galán-Cañete, Francisco Porcel-Pastrana, Jesús M Pérez-Gómez, María Ortega-Bellido, Julia Carrasco-Valiente, Laura Chamorro-Castillo, Juan P Campos-Hernández, Oriol A Rangel-Zuñiga, Teresa González-Serrano, Rafael Sánchez-Sánchez, André Sarmento-Cabral, Manuel D Gahete, Juan M Jiménez-Vacas, Raúl M Luque","doi":"10.1016/j.omton.2024.200910","DOIUrl":"https://doi.org/10.1016/j.omton.2024.200910","url":null,"abstract":"Prostate cancer (PCa) is the second most common cancer among men worldwide. The main screening tool remains the prostate-specific antigen (PSA), which shows significant limitations, including poor sensitivity/specificity. Therefore, establishing accurate non-invasive diagnostic biomarkers remains an unmet clinical need in PCa. In this context, the splicing process dysregulation represents a PCa hallmark. Here, plasma SRRM1, SNRNP200, and SRSF3 levels, previously identified to play a pathophysiological role in PCa, were determined in control individuals (n = 40) and PCa patients (n = 166). We found that plasma SRRM1 and SNRNP200 levels were elevated in PCa patients and discriminated between control individuals and PCa patients. High plasma SRRM1 levels were associated with a shorter castration-resistant PCa-free survival and correlated with androgen-receptor (AR)/AR-splicing variant 7 (AR-V7) expression levels and activity in PCa tissues. Therefore, the functional and molecular effects of in vivo SRRM1 silencing were then tested in 22Rv1-derived xenograft tumors. In vivo SRRM1 silencing reduced aggressiveness features and altered AR/AR-V7 activity. Our data reveal that SRRM1 holds potential as a non-invasive diagnostic and prognostic biomarker and novel therapeutic target in PCa, offering a clinically relevant opportunity worth exploring in humans.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"32 4","pages":"200910"},"PeriodicalIF":0.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934398","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

An oncolytic HAdV-5 with reduced surface charge combines diminished toxicity and improved tumor targeting. 具有降低表面电荷的溶瘤性HAdV-5结合了降低毒性和提高肿瘤靶向性。

Molecular therapy. Oncology Pub Date : 2024-11-23 eCollection Date: 2024-12-19 DOI: 10.1016/j.omton.2024.200909

Frederik Wienen, Robin Nilson, Ellen Allmendinger, Sarah Peters, Thomas F E Barth, Stefan Kochanek, Lea Krutzke

{"title":"An oncolytic HAdV-5 with reduced surface charge combines diminished toxicity and improved tumor targeting.","authors":"Frederik Wienen, Robin Nilson, Ellen Allmendinger, Sarah Peters, Thomas F E Barth, Stefan Kochanek, Lea Krutzke","doi":"10.1016/j.omton.2024.200909","DOIUrl":"https://doi.org/10.1016/j.omton.2024.200909","url":null,"abstract":"Human adenovirus type 5 (HAdV-5)-based oncolytic viruses hold significant promise for anti-cancer therapy. However, poor tumor-targeting and off-target organ transduction after systemic administration limit their therapeutic efficacy. In addition, the strong liver tropism of HAdV-5-based vectors poses the risk of hepatotoxicity. By genetic modification of the major capsid protein hexon we generated a HAdV-5-based oncolytic vector (HAdV-5-HexPos3) with reduced negative surface charge. Coxsackie and adenovirus receptor (CAR) binding-ablated (ΔCAR) HAdV-5-HexPos3_ΔCAR exhibited superior and CAR-independent transduction of various cancer cell lines in vitro, further enhanced in the presence of HAdV-5 naive murine plasma. Upon intravenous administration into tumor-bearing immunodeficient NSG mice, replication-deficient HAdV-5-HexPos3_ΔCAR vector particles showed significantly reduced off-target organ tropism in all tissues analyzed, including the liver. Moreover, we detected a significantly increased intratumoral vector load for HAdV-5-HexPos3_ΔCAR, leading to a 29-fold elevated tumor-to-liver ratio compared with a control vector with unmodified hexon. Intravenous injection of a conditionally replicating hexon-unmodified control vector induced severe hepatotoxicity in tumor-bearing NSG mice, while a conditionally replicating HAdV-5-HexPos3_ΔCAR vector was well tolerated and resulted in intratumoral vector presence for up to 56 days. HAdV-5-HexPos3_ΔCAR represents a promising vector platform for the generation of HAdV-5-based oncolytic viruses with reduced systemic toxicity and improved therapeutic efficacy.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"32 4","pages":"200909"},"PeriodicalIF":0.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934397","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

Drug repurposing screen targeting PARP identifies cytotoxic activity of efavirenz in high-grade serous ovarian cancer. 以 PARP 为靶点的药物再利用筛选确定了依非韦伦在高级别浆液性卵巢癌中的细胞毒性活性。

Molecular therapy. Oncology Pub Date : 2024-11-23 eCollection Date: 2024-12-19 DOI: 10.1016/j.omton.2024.200911

Bayley Matthews, Michelle Wong-Brown, Dongli Liu, Christine Yee, Kristie-Ann Dickson, Jennifer Schneider, Saiful Islam, Richard Head, Jennifer H Martin, Caroline E Ford, Deborah J Marsh, Nikola A Bowden

{"title":"Drug repurposing screen targeting PARP identifies cytotoxic activity of efavirenz in high-grade serous ovarian cancer.","authors":"Bayley Matthews, Michelle Wong-Brown, Dongli Liu, Christine Yee, Kristie-Ann Dickson, Jennifer Schneider, Saiful Islam, Richard Head, Jennifer H Martin, Caroline E Ford, Deborah J Marsh, Nikola A Bowden","doi":"10.1016/j.omton.2024.200911","DOIUrl":"10.1016/j.omton.2024.200911","url":null,"abstract":"Drug repurposing has potential to improve outcomes for high-grade serous ovarian cancer (HGSOC). Repurposing drugs with PARP family binding activity may produce cytotoxic effects through the multiple mechanisms of PARP including DNA repair, cell-cycle regulation, and apoptosis. The aim of this study was to determine existing drugs that have PARP family binding activity and can be repurposed for treatment of HGSOC. In silico ligand-based virtual screening (BLAZE) was used to identify drugs with potential PARP-binding activity. The list was refined by dosing, known cytotoxicity, lipophilicity, teratogenicity, and side effects. The highest ranked drug, efavirenz, progressed to in vitro testing. Molecularly characterized HGSOC cell lines, 3D hydrogel-encapsulated models, and patient-derived organoid models were used to determine the IC50 for efavirenz, cell death, apoptosis, PARP1 enzyme expression, and activity in intact cancer cells following efavirenz treatment. The IC50 for efavirenz was 26.43-45.85 μM for cells in two dimensions; 27.81 μM-54.98 μM in three dimensions, and 14.52 μM-42.27 μM in HGSOC patient-derived organoids. Efavirenz decreased cell viability via inhibition of PARP; increased CHK2 and phosphor-RB; increased cell-cycle arrest via decreased CDK2; increased γH2AX, DNA damage, and apoptosis. The results of this study suggest that efavirenz may be a viable treatment for HGSOC.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"32 4","pages":"200911"},"PeriodicalIF":0.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11719850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974313","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

Optimized protocol for culturing menstrual blood-derived MSCs for combination with oncolytic adenoviruses in cancer treatment. 经血来源间充质干细胞与溶瘤腺病毒联合用于癌症治疗的优化方案。

Molecular therapy. Oncology Pub Date : 2024-11-20 eCollection Date: 2024-12-19 DOI: 10.1016/j.omton.2024.200907

Marcel Costa-Garcia, Laura Moya-Borrego, Ramon Alemany Bonastre, Rafael Moreno Olié

{"title":"Optimized protocol for culturing menstrual blood-derived MSCs for combination with oncolytic adenoviruses in cancer treatment.","authors":"Marcel Costa-Garcia, Laura Moya-Borrego, Ramon Alemany Bonastre, Rafael Moreno Olié","doi":"10.1016/j.omton.2024.200907","DOIUrl":"https://doi.org/10.1016/j.omton.2024.200907","url":null,"abstract":"Oncolytic viruses (OVs) are a promising therapeutic approach for cancer, although their systemic administration faces significant challenges. Mesenchymal stem cells have emerged as potential carriers to overcome these obstacles due to their tumor-tropic properties. This study investigates the use of menstrual blood-derived mesenchymal stem cells (MenSCs) as carriers for OVs in cancer therapy, focusing on enhancing their efficacy through different culture conditions. MenSCs were isolated from donors of different ages and cultured under normoxic and hypoxic conditions, with varying adherence capacities. Hypoxic conditions significantly improved MenSCs proliferation and tumor migration capabilities, as demonstrated by proliferation assays and RNA-sequencing analysis, which revealed upregulation of genes related to cell division and tumor tropism. In vivo studies using a lung adenocarcinoma mouse model confirmed that hypoxia-conditioned MenSCs had superior tumor-homing abilities. The study also demonstrated the feasibility of establishing a master and working cell bank from a single menstrual blood donation. These findings suggest that hypoxia-conditioned MenSCs could be highly effective as OV carriers, potentially leading to better clinical outcomes in cancer treatment by enhancing tumor targeting and therapeutic efficacy.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"32 4","pages":"200907"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934337","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

Virus replication is not required for oncolytic bovine herpesvirus-1 immunotherapy. 溶瘤牛疱疹病毒-1 免疫疗法不需要病毒复制。

Molecular therapy. Oncology Pub Date : 2024-11-18 eCollection Date: 2024-12-19 DOI: 10.1016/j.omton.2024.200906

Enzo Mongiovi Baracuhy, Olga Cormier, Maria Eugenia Davola, Susan Collins, Karen Mossman

{"title":"Virus replication is not required for oncolytic bovine herpesvirus-1 immunotherapy.","authors":"Enzo Mongiovi Baracuhy, Olga Cormier, Maria Eugenia Davola, Susan Collins, Karen Mossman","doi":"10.1016/j.omton.2024.200906","DOIUrl":"10.1016/j.omton.2024.200906","url":null,"abstract":"Oncolytic viruses are a promising approach for cancer treatment where viruses selectively target and kill cancer cells while also stimulating an immune response. Among viruses with this ability, bovine herpesvirus-1 (BoHV-1) has several advantages, including observations suggesting it may not require viral replication for its anti-cancer effects. We previously demonstrated that binding and penetration of enveloped virus particles are sufficient to trigger intrinsic and innate immune signaling in normal cells, while other groups have published the efficacy of non-replicating viruses as viable immunotherapies in different cancer models. In this work, we definitively show that live and UV-inactivated (UV) (non-replicating) BoHV-1-based regimens extend survival of tumor-bearing mice to similar degrees and induce infiltration of similar immune cell populations, with the exception of neutrophils. Transcriptomic analysis of tumors treated with either live or UV BoHV-1-based regimens revealed similar pathway enrichment and a subset of overlapping differentially regulated genes, suggesting live and UV BoHV-1 have similar mechanisms of activity. Last, we present a gene signature across our in vitro and in vivo models that could potentially be used to validate new BoHV-1 therapeutics. This work contributes to the growing body of literature showing that replication may not be necessary for therapeutic efficacy of viral immunotherapies.","PeriodicalId":519884,"journal":{"name":"Molecular therapy. Oncology","volume":"32 4","pages":"200906"},"PeriodicalIF":0.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11650296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848004","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