Molecular Therapy Oncolytics最新文献_第8页

Next generation oncolytic viruses expressing PADI1 and TIMP2 exhibit anti-tumor activity against melanoma in nude and humanized mouse models. 在裸鼠和人源化小鼠模型中，表达PADI1和TIMP2的新一代溶瘤病毒显示出抗黑色素瘤的活性。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2023.01.002

Lukasz Kuryk, Anne-Sophie W Møller

{"title":"Next generation oncolytic viruses expressing PADI1 and TIMP2 exhibit anti-tumor activity against melanoma in nude and humanized mouse models.","authors":"Lukasz Kuryk, Anne-Sophie W Møller","doi":"10.1016/j.omto.2023.01.002","DOIUrl":"https://doi.org/10.1016/j.omto.2023.01.002","url":null,"abstract":"Immunotherapy of metastatic melanoma (MM) has vastly improved the longevity of only a minority of patients. To broaden the repertoire of agents against MM, we investigated the effectiveness of locally interrupting tumor blood endothelial cell proliferation and angiogenesis, arginine deprivation, or both on the growth of melanoma by constructing and characterizing the effectiveness of four oncolytic adenoviruses. ONCOS-207 (which expressed tissue inhibitor of metalloprotease type 2 [TIMP2]), ONCOS-209 (which expressed peptidyl arginine deiminase [PADI1]), and ONCOS-210 and ONCOS-212 (which expressed both TIMP2 and PADI1) exhibited oncolytic activity against four melanoma cell lines in vitro. ONCOS-212 treatments significantly inhibited tumor growth in an A2058 tumor model in nude mice compared with vehicle control. The inhibitory effects of the two transgenes of ONCOS-212 on tumor growth appeared to be synergistic. These viruses also significantly inhibited tumor growth in a humanized NOG model of melanoma (A2058 xenograft). All viruses significantly increased the percentage of activated CD8+ T cells in the tumor-infiltrating lymphocytes. The abscopal effect of ONCOS-212 treatments in the A2058 tumor challenge model in hNOG mice supports the hypothesis that the human immune response contributes to the anti-tumor activity of ONCOS-212. These results support the further development of ONCOS-212 for cancer treatment.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"28 ","pages":"158-170"},"PeriodicalIF":5.7,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10755257","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

Breast cancer tumor microenvironment affects Treg/IL-17-producing Treg/Th17 cell axis: Molecular and therapeutic perspectives. 乳腺癌肿瘤微环境影响Treg/ il -17生成Treg/Th17细胞轴:分子和治疗观点

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2023.01.001

Farhad Seif, Zahra Torki, Hamidreza Zalpoor, Mehran Habibi, Majid Pornour

{"title":"Breast cancer tumor microenvironment affects Treg/IL-17-producing Treg/Th17 cell axis: Molecular and therapeutic perspectives.","authors":"Farhad Seif, Zahra Torki, Hamidreza Zalpoor, Mehran Habibi, Majid Pornour","doi":"10.1016/j.omto.2023.01.001","DOIUrl":"https://doi.org/10.1016/j.omto.2023.01.001","url":null,"abstract":"The tumor microenvironment (TME) comprises a variety of immune cells, among which T cells exert a prominent axial role in tumor development or anti-tumor responses in patients with breast cancer (BC). High or low levels of anti-inflammatory cytokines, such as transforming growth factor β, in the absence or presence of proinflammatory cytokines, such as interleukin-6 (IL-6), delineate the fate of T cells toward either regulatory T (Treg) or T helper 17 (Th17) cells, respectively. The transitional state of RORγt+Foxp3+ Treg (IL-17-producing Treg) resides in the middle of this reciprocal polarization, which is known as Treg/IL-17-producing Treg/Th17 cell axis. TME secretome, including microRNAs, cytokines, and extracellular vesicles, can significantly affect this axis. Furthermore, immune checkpoint inhibitors may be used to reconstruct immune cells; however, some of these novel therapies may favor tumor development. Therefore, understanding secretory and cell-associated factors involved in their differentiation or polarization and functions may be targeted for BC management. This review discusses microRNAs, cytokines, and extracellular vesicles (as secretome), as well as transcription factors and immune checkpoints (as cell-associated factors), which influence the Treg/IL-17-producing Treg/Th17 cell axis in BC. Furthermore, approved or ongoing clinical trials related to the modulation of this axis in the TME of BC are described to broaden new horizons of promising therapeutic approaches.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"28 ","pages":"132-157"},"PeriodicalIF":5.7,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10767181","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: 10

Overcoming resistance of stroma-rich pancreatic cancer with focal adhesion kinase inhibitor combined with G47Δ and immune checkpoint inhibitors. 局灶黏附激酶抑制剂联合G47Δ和免疫检查点抑制剂克服富间质胰腺癌的耐药性。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2022.12.001

Tomoharu Yamada, Ryosuke Tateishi, Miwako Iwai, Minoru Tanaka, Hideaki Ijichi, Makoto Sano, Kazuhiko Koike, Tomoki Todo

{"title":"Overcoming resistance of stroma-rich pancreatic cancer with focal adhesion kinase inhibitor combined with G47Δ and immune checkpoint inhibitors.","authors":"Tomoharu Yamada, Ryosuke Tateishi, Miwako Iwai, Minoru Tanaka, Hideaki Ijichi, Makoto Sano, Kazuhiko Koike, Tomoki Todo","doi":"10.1016/j.omto.2022.12.001","DOIUrl":"https://doi.org/10.1016/j.omto.2022.12.001","url":null,"abstract":"Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease known for its dense tumor stroma. Focal adhesion kinase inhibitor (FAKi), a non-receptor type tyrosine kinase inhibitor, reduces the tumor stroma. G47Δ, a third-generation oncolytic herpes simplex virus type 1, destroys tumor cells selectively and induces antitumor immune responses. This study evaluates the efficacy of FAKi and G47Δ in PDAC models in combination with or without immune checkpoint inhibitors. G47Δ was effective in human PDAC cell lines in vitro and in subcutaneous as well as orthotopic tumor models. Transgenic mouse-derived #146 cells were used to generate subcutaneous PDAC tumors with rich stroma in immunocompetent mice. In this #146 tumor model, the efficacy of FAKi was synergistically augmented when combined with G47Δ, which reflected not only a decreased stromal content but also a significant shifting of the tumor microenvironment toward immune stimulation. In transgenic autochthonous PKF mice, a rare model that develops stroma-rich PDAC with a 100% penetrance and resembles human PDAC in various aspects, the prolongation of survival compared with FAKi alone was achieved only when FAKi was combined with G47Δ and immune checkpoint inhibitors. The FAKi combination therapy may be useful to overcome the treatment resistance of stroma-rich PDAC.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"28 ","pages":"31-43"},"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/ed/c2/main.PMC9801088.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10513367","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

Seneca Valley virus replicons are packaged in trans and have the capacity to overcome the limitations of viral transgene expression. 塞内卡谷病毒复制子包装在反式中，具有克服病毒转基因表达限制的能力。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2023.02.005

Jeffrey D Bryant, Jennifer S Lee, Ana De Almeida, Judy Jacques, Ching-Hung Chang, William Fassler, Christophe Quéva, Lorena Lerner, Edward M Kennedy

{"title":"Seneca Valley virus replicons are packaged in trans and have the capacity to overcome the limitations of viral transgene expression.","authors":"Jeffrey D Bryant, Jennifer S Lee, Ana De Almeida, Judy Jacques, Ching-Hung Chang, William Fassler, Christophe Quéva, Lorena Lerner, Edward M Kennedy","doi":"10.1016/j.omto.2023.02.005","DOIUrl":"https://doi.org/10.1016/j.omto.2023.02.005","url":null,"abstract":"Oncolytic viruses (OVs) promote the anti-tumor immune response as their replication, and the subsequent lysis of tumor cells, triggers the activation of immune-sensing pathways. Arming OVs by expressing transgenes with the potential to promote immune cell recruitment and activation is an attractive strategy to enhance OVs' therapeutic benefit. For picornaviruses, a family of OVs with clinical experience, the expression of a transgene is limited by multiple factors: genome physical packaging limits, high rates of recombination, and viral-mediated inhibition of transgene secretion. Here, we evaluated strategies for arming Seneca Valley virus (SVV) with relevant immunomodulatory transgenes. Specificially in the contex of arming SVV, we evaluated transgene maximum size and stabiltity, transgene secretion, and the impact of transgene inclusion on viral fitness. We find that SVV is not capable of expressing secreted payloads and has a transgene packaging capacity of ∼10% of viral genome size. To enable transgene expression, we developed SVV replicons with greater transgene size capacity and secretion capabilities. SVV replicons can be packaged in trans by virus in co-infected cells to express immunomodulatory transgenes in surrounding cells, thus providing a means to enhance the potential of this therapeutic to augment the anti-tumor immune response.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"28 ","pages":"321-333"},"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/62/0d/main.PMC10018389.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9500429","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: 0

A novel chemical attack on Notch-mediated transcription by targeting the NACK ATPase. 针对NACK atp酶的notch介导转录的新化学攻击。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2023.02.008

Giulia Diluvio, Tanya T Kelley, Mohini Lahiry, Annamil Alvarez-Trotta, Ellen M Kolb, Elena Shersher, Luisana Astudillo, Rhett A Kovall, Stephan C Schürer, Anthony J Capobianco

引用次数: 1

Targeting carcinoembryonic antigen-expressing tumors using a novel transcriptional and translational dual-regulated oncolytic herpes simplex virus type 1. 利用一种新的转录和翻译双调控的溶瘤性单纯疱疹病毒1型靶向表达癌胚抗原的肿瘤。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2023.02.003

Dmitry V Chouljenko, Yanal M Murad, I-Fang Lee, Zahid Delwar, Jun Ding, Guoyu Liu, Xiaohu Liu, Xuexian Bu, Yi Sun, Ismael Samudio, William Wei-Guo Jia

{"title":"Targeting carcinoembryonic antigen-expressing tumors using a novel transcriptional and translational dual-regulated oncolytic herpes simplex virus type 1.","authors":"Dmitry V Chouljenko, Yanal M Murad, I-Fang Lee, Zahid Delwar, Jun Ding, Guoyu Liu, Xiaohu Liu, Xuexian Bu, Yi Sun, Ismael Samudio, William Wei-Guo Jia","doi":"10.1016/j.omto.2023.02.003","DOIUrl":"https://doi.org/10.1016/j.omto.2023.02.003","url":null,"abstract":"VG2025 is a recombinant oncolytic herpes simplex virus type 1 (HSV-1) that uses transcriptional and translational dual regulation (TTDR) of critical viral genes to enhance virus safety and promote tumor-specific virus replication without reducing virulence. The TTDR platform is based on transcriptional control of the essential HSV-1 immediate-early protein ICP27 using a tumor-specific carcinoembryonic antigen (CEA) promoter, coupled with translational control of the neurovirulence factor ICP34.5 using multiple microRNA (miR)-binding sites. VG2025 further incorporates IL-12 and the IL-15/IL-15 receptor alpha subunit complex to enhance the antitumor and immune stimulatory properties of oncolytic HSVs. The TTDR strategy was verified in vitro and shown to be highly selective. Strong in vivo antitumor efficacy was observed following both intratumoral and intravenous administration. Clear abscopal and immune memory effects were also evident, indicating a robust antitumor immune response. Gene expression profiling of treated tumors revealed increased immune cell infiltration and activation of multiple immune-signaling pathways when compared with the backbone virus. Absence of neurotoxicity was verified in mice and in rhesus monkeys. Taken together, the enhanced tumor clearance, excellent safety profile, and positive correlation between CEA levels and viral replication efficiency may provide an opportunity for using biomarker-based precision medicine in oncolytic virotherapy.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"28 ","pages":"334-348"},"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/65/c3/main.PMC10018392.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516047","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

Zika virus cleaves GSDMD to disseminate prognosticable and controllable oncolysis in a human glioblastoma cell model. 在人类胶质母细胞瘤细胞模型中，寨卡病毒切割GSDMD传播可预测和可控的肿瘤溶解。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2022.12.008

Yu-Ting Kao, Hsin-I Wang, Chi-Ting Shie, Chiou-Feng Lin, Michael M C Lai, Chia-Yi Yu

{"title":"Zika virus cleaves GSDMD to disseminate prognosticable and controllable oncolysis in a human glioblastoma cell model.","authors":"Yu-Ting Kao, Hsin-I Wang, Chi-Ting Shie, Chiou-Feng Lin, Michael M C Lai, Chia-Yi Yu","doi":"10.1016/j.omto.2022.12.008","DOIUrl":"https://doi.org/10.1016/j.omto.2022.12.008","url":null,"abstract":"Glioblastoma (GBM) is the most common aggressive malignant brain cancer and is chemo- and radioresistant, with poor therapeutic outcomes. The \"double-edged sword\" of virus-induced cell death could be a potential solution if the oncolytic virus specifically kills cancer cells but spares normal ones. Zika virus (ZIKV) has been defined as a prospective oncolytic virus by selectively targeting GBM cells, but unclear understanding of how ZIKV kills GBM and the consequences hinders its application. Here, we found that the cellular gasdermin D (GSDMD) is required for the efficient death of a human GBM cell line caused by ZIKV infection. The ZIKV protease specifically cleaves human GSDMD to activate caspase-independent pyroptosis, harming both viral protease-harboring and naive neighboring cells. Analyzing human GSDMD variants showed that most people were susceptible to ZIKV-induced cytotoxicity, except for those with variants that resisted ZIKV cleavage or were defective in oligomerizing the N terminus GSDMD cleavage product. Consistently, ZIKV-induced secretion of the pro-inflammatory cytokine interleukin-1β and cytolytic activity were both stopped by a small-molecule inhibitor targeting GSDMD oligomerization. Thus, potential ZIKV oncolytic therapy for GBM would depend on the patient's GSDMD genetic background and could be abolished by GSDMD inhibitors if required.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"28 ","pages":"104-117"},"PeriodicalIF":5.7,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9178067","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: 3

Development of a 5-FU modified miR-129 mimic as a therapeutic for non-small cell lung cancer. 5-FU修饰的miR-129模拟物作为非小细胞肺癌治疗的发展

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2023.02.007

Ga-Ram Hwang, John G Yuen, Andrew Fesler, Hannah Farley, John D Haley, Jingfang Ju

{"title":"Development of a 5-FU modified miR-129 mimic as a therapeutic for non-small cell lung cancer.","authors":"Ga-Ram Hwang, John G Yuen, Andrew Fesler, Hannah Farley, John D Haley, Jingfang Ju","doi":"10.1016/j.omto.2023.02.007","DOIUrl":"https://doi.org/10.1016/j.omto.2023.02.007","url":null,"abstract":"Lung cancer is the leading cause of cancer-related deaths in the United States with non-small cell lung cancer (NSCLC) accounting for most cases. Despite advances in cancer therapeutics, the 5-year survival rate has remained poor due to several contributing factors, including its resistance to therapeutics. Therefore, there is a pressing need to develop therapeutics that can overcome resistance. Non-coding RNAs, including microRNAs (miRNAs), have been found to contribute to cancer resistance and therapeutics by modulating the expression of several targets involving multiple key mechanisms. In this study, we investigated the therapeutic potential of miR-129 modified with 5-fluorouracil (5-FU) in NSCLC. Our results show that 5-FU modified miR-129 (5-FU-miR-129) inhibits proliferation, induces apoptosis, and retains function as an miRNA in NSCLC cell lines A549 and Calu-1. Notably, we observed that 5-FU-miR-129 was able to overcome resistance to tyrosine kinase inhibitors and chemotherapy in cell lines resistant to erlotinib or 5-FU. Furthermore, we observed that the inhibitory effect of 5-FU-miR-129 can also be achieved in NSCLC cells under vehicle-free conditions. Finally, 5-FU-miR-129 inhibited NSCLC tumor growth and extended survival in vivo without toxic side effects. Altogether, our results demonstrate the potential of 5-FU-miR-129 as a highly potent cancer therapeutic in NSCLC.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"28 ","pages":"277-292"},"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/2f/2c/main.PMC9995506.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9102587","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: 1

Oncogenic lncRNA BBOX1-AS1 promotes PHF8-mediated autophagy and elicits sorafenib resistance in hepatocellular carcinoma. 致癌lncRNA BBOX1-AS1在肝细胞癌中促进phf8介导的自噬并引发索拉非尼耐药。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2022.12.005

Haisu Tao, Yuxin Zhang, Jiang Li, Junjie Liu, Tong Yuan, Wenqiang Wang, Huifang Liang, Erlei Zhang, Zhiyong Huang

{"title":"Oncogenic lncRNA BBOX1-AS1 promotes PHF8-mediated autophagy and elicits sorafenib resistance in hepatocellular carcinoma.","authors":"Haisu Tao, Yuxin Zhang, Jiang Li, Junjie Liu, Tong Yuan, Wenqiang Wang, Huifang Liang, Erlei Zhang, Zhiyong Huang","doi":"10.1016/j.omto.2022.12.005","DOIUrl":"https://doi.org/10.1016/j.omto.2022.12.005","url":null,"abstract":"Some long non-coding RNAs (lncRNAs) have been documented to be involved in cancer progression and anticancer drug resistance in hepatocellular carcinoma (HCC). Thus, approaches designed to target these genes may facilitate the development of promising strategies for treating HCC. Previously, we showed that lncRNA BBOX1-AS1 was highly expressed and played an oncogenic role in HCC. However, the potential functions and mechanisms through which BBOX1-AS1 regulates HCC progression and drug resistance remain unclear. This study revealed that BBOX1-AS1 could promote tumor progression, autophagy, and drug resistance by upregulating PHF8 in HCC cells. Mechanistically, BBOX1-AS1 enhanced the stability of PHF8 mRNA by targeting the PHF8 inhibitor miR-361-3p to regulate tumor progression and autophagy in HCC. The functional rescue experiments showed that PHF8 acted as a key factor in regulating the biological effects induced by BBOX1-AS1 and miR-361-3p in HCC, indicating that BBOX1-AS1 promotes tumor progression and sorafenib resistance by regulating miR-361-3p/PHF8. Finally, mouse tumor models and patient-derived organoid models were established to further confirm these findings. Taken together, the results demonstrate that BBOX1-AS1 promotes HCC progression and sorafenib resistance via the miR-361-3p/PHF8 axis.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"28 ","pages":"88-103"},"PeriodicalIF":5.7,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9852557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9191149","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: 5

Anti-tumor immunity enhancement by photodynamic therapy with talaporfin sodium and anti-programmed death 1 antibody. 他拉波芬钠光动力治疗与抗程序性死亡1抗体增强抗肿瘤免疫。

IF 5.7 2区医学

Molecular Therapy Oncolytics Pub Date : 2023-03-16 DOI: 10.1016/j.omto.2022.12.009

Makiko Sasaki, Mamoru Tanaka, Yuki Kojima, Hirotada Nishie, Takaya Shimura, Eiji Kubota, Hiromi Kataoka

{"title":"Anti-tumor immunity enhancement by photodynamic therapy with talaporfin sodium and anti-programmed death 1 antibody.","authors":"Makiko Sasaki, Mamoru Tanaka, Yuki Kojima, Hirotada Nishie, Takaya Shimura, Eiji Kubota, Hiromi Kataoka","doi":"10.1016/j.omto.2022.12.009","DOIUrl":"https://doi.org/10.1016/j.omto.2022.12.009","url":null,"abstract":"Photodynamic therapy (PDT) is a relatively non-invasive anti-cancer therapy that employs a photosensitizer with a specific wavelength of light irradiation. PDT induces direct cell killing and enhancement effects on tumor immunity, but its underlying mechanism remains unknown. Here, we perform a basic analysis of the anti-tumor effect of talaporfin sodium (TS)-PDT as well as its synergism with the immune checkpoint inhibitor anti-programmed death 1 (anti-PD-1) antibody. We estimate the cell death mechanism induced by TS-PDT and the induction of damage-associated molecular patterns (DAMPs) by TS-PDT in vitro. We establish a syngeneic mouse model of bilateral flank tumors and verify the enhancement of the abscopal effect on the non-irradiated side. TS-PDT induced apoptosis, necrosis, and autophagy-associated cell death in vitro. TS-PDT induced the release and/or expression of DAMPs in vitro. Tumor growth was inhibited in the TS-PDT and anti-PD-1 antibody combination group compared with other single-treatment or non-treatment groups in vivo. In summary, TS-PDT induces the release and/or expression of DAMPs, indicating that it activates innate immunity. PD-1 blockage enhances the anti-tumor immunity induced by TS-PDT. Thus, our results demonstrate that the combination of TS-PDT and anti-PD-1 antibody can potentially be used for anti-tumor therapy.","PeriodicalId":18869,"journal":{"name":"Molecular Therapy Oncolytics","volume":"28 ","pages":"118-131"},"PeriodicalIF":5.7,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9867957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9209022","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: 6