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  1. Article: Triple combination therapy for pancreatic cancer remodels stroma and improves survival.

    Vázquez-Arreguín, Karina / Kaur, Balveen

    Molecular therapy oncolytics

    2023  Volume 29, Page(s) 15–16

    Language English
    Publishing date 2023-03-21
    Publishing country United States
    Document type News
    ISSN 2372-7705
    ISSN 2372-7705
    DOI 10.1016/j.omto.2023.03.001
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  2. Article ; Online: Exogenous non-coding dsDNA-dependent trans-activation of phagocytes augments anti-tumor immunity.

    Delaunay, Tiphaine / Son, Sehee / Park, Seongji / Kaur, Balveen / Ahn, Jeonghyun / Barber, Glen N

    Cell reports. Medicine

    2024  , Page(s) 101528

    Abstract: Stimulator of interferon genes (STING)-dependent signaling is requisite for effective anti-microbial and anti-tumor activity. STING signaling is commonly defective in cancer cells, which enables tumor cells to evade the immunosurveillance system. We ... ...

    Abstract Stimulator of interferon genes (STING)-dependent signaling is requisite for effective anti-microbial and anti-tumor activity. STING signaling is commonly defective in cancer cells, which enables tumor cells to evade the immunosurveillance system. We evaluate here whether intrinsic STING signaling in such tumor cells could be reconstituted by creating recombinant herpes simplex viruses (rHSVs) that express components of the STING signaling pathway. We observe that rHSVs expressing STING and/or cGAS replicate inefficiently yet retain in vivo anti-tumor activity, independent of oncolytic activityrequisite on the trans-activation of extrinsic STING signaling in phagocytes by engulfed microbial dsDNA species. Accordingly, the in vivo effects of virotherapy could be simulated by nanoparticles incorporating non-coding dsDNA species, which comparably elicit the trans-activation of phagocytes and augment the efficacy of established cancer treatments including checkpoint inhibition and radiation therapy. Our results help elucidate mechanisms of virotherapeutic anti-tumor activity as well as provide alternate strategies to treat cancer.
    Language English
    Publishing date 2024-04-23
    Publishing country United States
    Document type Journal Article
    ISSN 2666-3791
    ISSN (online) 2666-3791
    DOI 10.1016/j.xcrm.2024.101528
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: oHSV-P10 reduces glioma stem cell enrichment after oncolytic HSV therapy.

    Sahu, Upasana / Mullarkey, Matthew P / Pei, Guangsheng / Zhao, Zhongming / Hong, Bangxing / Kaur, Balveen

    Molecular therapy oncolytics

    2023  Volume 29, Page(s) 30–41

    Abstract: Longstanding evidence implicate glioma stem-like cells as the main drivers contributing toward glioblastoma (GBM) therapy resistance and tumor recurrence. Although oncolytic herpes simplex virus (oHSV) viral therapy is a promising biological therapy ... ...

    Abstract Longstanding evidence implicate glioma stem-like cells as the main drivers contributing toward glioblastoma (GBM) therapy resistance and tumor recurrence. Although oncolytic herpes simplex virus (oHSV) viral therapy is a promising biological therapy recently approved for melanoma (in the United States and Europe) and GBM (in Japan); however, the impact of this therapy on GBM stem-like cells (GSCs) is understudied. Here we show that post-oHSV virotherapy activated AKT signaling results in an enrichment of GSC signatures in glioma, which mimics the enrichment in GSC observed after radiation treatment. We also uncovered that a second-generation oncolytic virus armed with PTEN-L (oHSV-P10) decreases this by moderating IL6/JAK/STAT3 signaling. This ability was retained in the presence of radiation treatment and oHSV-P10-sensitized intracranial GBM to radiotherapy. Collectively, our findings uncover potential mechanisms to overcome GSC-mediated radiation resistance via oHSV-P10.
    Language English
    Publishing date 2023-04-03
    Publishing country United States
    Document type Journal Article
    ISSN 2372-7705
    ISSN 2372-7705
    DOI 10.1016/j.omto.2023.03.003
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  4. Article ; Online: Replication and Spread of Oncolytic Herpes Simplex Virus in Solid Tumors.

    Hong, Bangxing / Sahu, Upasana / Mullarkey, Matthew P / Kaur, Balveen

    Viruses

    2022  Volume 14, Issue 1

    Abstract: Oncolytic herpes simplex virus (oHSV) is a highly promising treatment for solid tumors. Intense research and development efforts have led to first-in-class approval for an oHSV for melanoma, but barriers to this promising therapy still exist that limit ... ...

    Abstract Oncolytic herpes simplex virus (oHSV) is a highly promising treatment for solid tumors. Intense research and development efforts have led to first-in-class approval for an oHSV for melanoma, but barriers to this promising therapy still exist that limit efficacy. The process of infection, replication and transmission of oHSV in solid tumors is key to obtaining a good lytic destruction of infected cancer cells to kill tumor cells and release tumor antigens that can prime anti-tumor efficacy. Intracellular tumor cell signaling and tumor stromal cells present multiple barriers that resist oHSV activity. Here, we provide a review focused on oncolytic HSV and the essential viral genes that allow for virus replication and spread in order to gain insight into how manipulation of these pathways can be exploited to potentiate oHSV infection and replication among tumor cells.
    MeSH term(s) Animals ; Cell Line, Tumor ; Herpes Simplex ; Herpesvirus 1, Human/genetics ; Humans ; Neoplasms/therapy ; Oncolytic Virotherapy ; Oncolytic Viruses/genetics ; Tropism ; Virus Replication
    Language English
    Publishing date 2022-01-10
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14010118
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  5. Article ; Online: The Notch signaling pathway: a potential target for cancer immunotherapy.

    Li, Xinxin / Yan, Xianchun / Wang, Yufeng / Kaur, Balveen / Han, Hua / Yu, Jianhua

    Journal of hematology & oncology

    2023  Volume 16, Issue 1, Page(s) 45

    Abstract: Dysregulation of the Notch signaling pathway, which is highly conserved across species, can drive aberrant epigenetic modification, transcription, and translation. Defective gene regulation caused by dysregulated Notch signaling often affects networks ... ...

    Abstract Dysregulation of the Notch signaling pathway, which is highly conserved across species, can drive aberrant epigenetic modification, transcription, and translation. Defective gene regulation caused by dysregulated Notch signaling often affects networks controlling oncogenesis and tumor progression. Meanwhile, Notch signaling can modulate immune cells involved in anti- or pro-tumor responses and tumor immunogenicity. A comprehensive understanding of these processes can help with designing new drugs that target Notch signaling, thereby enhancing the effects of cancer immunotherapy. Here, we provide an up-to-date and comprehensive overview of how Notch signaling intrinsically regulates immune cells and how alterations in Notch signaling in tumor cells or stromal cells extrinsically regulate immune responses in the tumor microenvironment (TME). We also discuss the potential role of Notch signaling in tumor immunity mediated by gut microbiota. Finally, we propose strategies for targeting Notch signaling in cancer immunotherapy. These include oncolytic virotherapy combined with inhibition of Notch signaling, nanoparticles (NPs) loaded with Notch signaling regulators to specifically target tumor-associated macrophages (TAMs) to repolarize their functions and remodel the TME, combining specific and efficient inhibitors or activators of Notch signaling with immune checkpoint blockers (ICBs) for synergistic anti-tumor therapy, and implementing a customized and effective synNotch circuit system to enhance safety of chimeric antigen receptor (CAR) immune cells. Collectively, this review aims to summarize how Notch signaling intrinsically and extrinsically shapes immune responses to improve immunotherapy.
    MeSH term(s) Humans ; Immunotherapy ; Neoplasms/pathology ; Antigens, Neoplasm/pharmacology ; Nanoparticles ; Signal Transduction ; Tumor Microenvironment
    Chemical Substances Antigens, Neoplasm
    Language English
    Publishing date 2023-05-02
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2429631-4
    ISSN 1756-8722 ; 1756-8722
    ISSN (online) 1756-8722
    ISSN 1756-8722
    DOI 10.1186/s13045-023-01439-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Histone modifiers at the crossroads of oncolytic and oncogenic viruses.

    Murphy, Sara A / Mapes, Norman John / Dua, Devika / Kaur, Balveen

    Molecular therapy : the journal of the American Society of Gene Therapy

    2022  Volume 30, Issue 6, Page(s) 2153–2162

    Abstract: Cancer is a disease caused by loss of regulatory processes that control the cell cycle, resulting in increased proliferation. The loss of control can deregulate both tumor suppressors and oncogenes. Apart from cell intrinsic gene mutations and ... ...

    Abstract Cancer is a disease caused by loss of regulatory processes that control the cell cycle, resulting in increased proliferation. The loss of control can deregulate both tumor suppressors and oncogenes. Apart from cell intrinsic gene mutations and environmental factors, infection by cancer-causing viruses also induces changes that lead to malignant transformation. This can be caused by both expression of oncogenic viral proteins and also by changes in cellular genes and proteins that affect the epigenome. Thus, these epigenetic modifiers are good therapeutic targets, and several epigenetic inhibitors are approved for the treatment of different cancers. In addition to small molecule drugs, biological therapies, such as antibodies and viral therapies, are also increasingly being used to treat cancer. An HSV-1-derived oncolytic virus is currently approved by the US FDA and the European Medicines Agency. Similarly, an adenovirus-based therapeutic is approved for use in China for some cancer types. Because viruses can affect cellular epigenetics, the interaction of epigenome-targeting drugs with oncogenic and oncolytic viruses is a highly significant area of investigation. Here, we will review the current knowledge about the impact of using epigenetic drugs in tumors positive for oncogenic viruses or as therapeutic combinations with oncolytic viruses.
    MeSH term(s) Histones/genetics ; Humans ; Neoplasms/genetics ; Neoplasms/therapy ; Oncogenic Viruses/genetics ; Oncolytic Virotherapy ; Oncolytic Viruses/genetics
    Chemical Substances Histones
    Language English
    Publishing date 2022-02-08
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1016/j.ymthe.2022.02.006
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  7. Article ; Online: Immune therapy, a double-edged sword for oncolytic viruses.

    McCormack, Ryan M / Kaur, Balveen

    Expert opinion on biological therapy

    2019  Volume 19, Issue 11, Page(s) 1111–1113

    Language English
    Publishing date 2019-08-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2052501-1
    ISSN 1744-7682 ; 1471-2598
    ISSN (online) 1744-7682
    ISSN 1471-2598
    DOI 10.1080/14712598.2019.1650911
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  8. Article ; Online: Implications of immune cells in oncolytic herpes simplex virotherapy for glioma.

    Otani, Yoshihiro / Yoo, Ji Young / Shimizu, Toshihiko / Kurozumi, Kazuhiko / Date, Isao / Kaur, Balveen

    Brain tumor pathology

    2022  Volume 39, Issue 2, Page(s) 57–64

    Abstract: Despite current progress in treatment, glioblastoma (GBM) remains a lethal primary malignant tumor of the central nervous system. Although immunotherapy has recently achieved remarkable survival effectiveness in multiple malignancies, none of the immune ... ...

    Abstract Despite current progress in treatment, glioblastoma (GBM) remains a lethal primary malignant tumor of the central nervous system. Although immunotherapy has recently achieved remarkable survival effectiveness in multiple malignancies, none of the immune checkpoint inhibitors (ICIs) for GBM have shown anti-tumor efficacy in clinical trials. GBM has a characteristic immunosuppressive tumor microenvironment (TME) that results in the failure of ICIs. Oncolytic herpes simplex virotherapy (oHSV) is the most advanced United States Food and Drug Administration-approved virotherapy for advanced metastatic melanoma patients. Recently, another oHSV, Delytact
    MeSH term(s) Glioblastoma/therapy ; Glioma/therapy ; Herpes Simplex/therapy ; Humans ; Oncolytic Virotherapy/methods ; Simplexvirus/genetics ; Tumor Microenvironment
    Language English
    Publishing date 2022-04-06
    Publishing country Japan
    Document type Journal Article ; Review
    ZDB-ID 1193775-0
    ISSN 1861-387X ; 1433-7398 ; 0914-8108
    ISSN (online) 1861-387X
    ISSN 1433-7398 ; 0914-8108
    DOI 10.1007/s10014-022-00431-8
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  9. Article: The complex relationship between integrins and oncolytic herpes Simplex Virus 1 in high-grade glioma therapeutics.

    Rivera-Caraballo, Kimberly Ann / Nair, Mitra / Lee, Tae Jin / Kaur, Balveen / Yoo, Ji Young

    Molecular therapy oncolytics

    2022  Volume 26, Page(s) 63–75

    Abstract: High-grade gliomas (HGGs) are lethal central nervous system tumors that spread quickly through the brain, making treatment challenging. Integrins are transmembrane receptors that mediate cell-extracellular matrix (ECM) interactions, cellular adhesion, ... ...

    Abstract High-grade gliomas (HGGs) are lethal central nervous system tumors that spread quickly through the brain, making treatment challenging. Integrins are transmembrane receptors that mediate cell-extracellular matrix (ECM) interactions, cellular adhesion, migration, growth, and survival. Their upregulation and inverse correlation in HGG malignancy make targeting integrins a viable therapeutic option. Integrins also play a role in herpes simplex virus 1 (HSV-1) entry. Oncolytic HSV-1 (oHSV) is the most clinically advanced oncolytic virotherapy, showing a superior safety and efficacy profile over standard cancer treatment of solid cancers, including HGG. With the FDA-approval of oHSV for melanoma and the recent conditional approval of oHSV for malignant glioma in Japan, usage of oHSV for HGG has become of great interest. In this review, we provide a systematic overview of the role of integrins in relation to oHSV, with a special focus on its therapeutic potential against HGG. We discuss the pros and cons of targeting integrins during oHSV therapy: while integrins play a pro-therapeutic role by acting as a gateway for oHSV entry, they also mediate the innate antiviral immune responses that hinder oHSV therapeutic efficacy. We further discuss alternative strategies to regulate the dual functionality of integrins in the context of oHSV therapy.
    Language English
    Publishing date 2022-06-06
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2372-7705
    ISSN 2372-7705
    DOI 10.1016/j.omto.2022.05.013
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  10. Article ; Online: Rat and Mouse Brain Tumor Models for Experimental Neuro-Oncology Research.

    Sahu, Upasana / Barth, Rolf F / Otani, Yoshihiro / McCormack, Ryan / Kaur, Balveen

    Journal of neuropathology and experimental neurology

    2022  Volume 81, Issue 5, Page(s) 312–329

    Abstract: Rodent brain tumor models have been useful for developing effective therapies for glioblastomas (GBMs). In this review, we first discuss the 3 most commonly used rat brain tumor models, the C6, 9L, and F98 gliomas, which are all induced by repeated ... ...

    Abstract Rodent brain tumor models have been useful for developing effective therapies for glioblastomas (GBMs). In this review, we first discuss the 3 most commonly used rat brain tumor models, the C6, 9L, and F98 gliomas, which are all induced by repeated injections of nitrosourea to adult rats. The C6 glioma arose in an outbred Wistar rat and its potential to evoke an alloimmune response is a serious limitation. The 9L gliosarcoma arose in a Fischer rat and is strongly immunogenic, which must be taken into consideration when using it for therapy studies. The F98 glioma may be the best of the 3 but it does not fully recapitulate human GBMs because it is weakly immunogenic. Next, we discuss a number of mouse models. The first are human patient-derived xenograft gliomas in immunodeficient mice. These have failed to reproduce the tumor-host interactions and microenvironment of human GBMs. Genetically engineered mouse models recapitulate the molecular alterations of GBMs in an immunocompetent environment and "humanized" mouse models repopulate with human immune cells. While the latter are rarely isogenic, expensive to produce, and challenging to use, they represent an important advance. The advantages and limitations of each of these brain tumor models are discussed. This information will assist investigators in selecting the most appropriate model for the specific focus of their research.
    MeSH term(s) Animals ; Brain Neoplasms/pathology ; Cell Line, Tumor ; Disease Models, Animal ; Glioblastoma ; Glioma/pathology ; Gliosarcoma ; Humans ; Mice ; Rats ; Rats, Wistar ; Tumor Microenvironment
    Language English
    Publishing date 2022-04-21
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 3088-0
    ISSN 1554-6578 ; 0022-3069
    ISSN (online) 1554-6578
    ISSN 0022-3069
    DOI 10.1093/jnen/nlac021
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