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  1. Article: MicroRNA-sensitive oncolytic measles virus for chemovirotherapy of pancreatic cancer.

    Singh, Hans Martin / Leber, Mathias Felix / Bossow, Sascha / Engeland, Christine E / Dessila, Jan / Grossardt, Christian / Zaoui, Karim / Bell, John C / Jäger, Dirk / von Kalle, Christof / Ungerechts, Guy

    Molecular therapy oncolytics

    2021  Volume 21, Page(s) 340–355

    Abstract: Advanced pancreatic cancer is characterized by few treatment options and poor outcomes. Oncolytic virotherapy and chemotherapy involve complementary pharmacodynamics and could synergize to improve therapeutic efficacy. Likewise, multimodality treatment ... ...

    Abstract Advanced pancreatic cancer is characterized by few treatment options and poor outcomes. Oncolytic virotherapy and chemotherapy involve complementary pharmacodynamics and could synergize to improve therapeutic efficacy. Likewise, multimodality treatment may cause additional toxicity, and new agents have to be safe. Balancing both aims, we generated an oncolytic measles virus for 5-fluorouracil-based chemovirotherapy of pancreatic cancer with enhanced tumor specificity through microRNA-regulated vector tropism. The resulting vector encodes a bacterial prodrug convertase, cytosine deaminase-uracil phosphoribosyl transferase, and carries synthetic miR-148a target sites in the viral
    Language English
    Publishing date 2021-05-05
    Publishing country United States
    Document type Journal Article
    ISSN 2372-7705
    ISSN 2372-7705
    DOI 10.1016/j.omto.2021.04.015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Sequencing of serially passaged measles virus affirms its genomic stability and reveals a nonrandom distribution of consensus mutations.

    Leber, Mathias Felix / Hoyler, Birgit / Prien, Stefanie / Neault, Serge / Engeland, Christine E / Förster, Judith M / Bossow, Sascha / Springfeld, Christoph / von Kalle, Christof / Jäger, Dirk / Bell, John C / Ungerechts, Guy

    The Journal of general virology

    2020  Volume 101, Issue 4, Page(s) 399–409

    Abstract: Oncolytic virotherapy is an emerging treatment option for numerous cancers, with several virus families currently being evaluated in clinical trials. More specifically, vaccine-strain measles virus has arisen as a promising candidate for the treatment of ...

    Abstract Oncolytic virotherapy is an emerging treatment option for numerous cancers, with several virus families currently being evaluated in clinical trials. More specifically, vaccine-strain measles virus has arisen as a promising candidate for the treatment of different tumour types in several early clinical trials. Replicating viruses, and especially RNA viruses without proofreading polymerases, can rapidly adapt to varying environments by selecting quasispecies with advantageous genetic mutations. Subsequently, these genetic alterations could potentially weaken the safety profile of virotherapy. In this study, we demonstrate that, following an extended period of virus replication in producer or cancer cell lines, the quasispecies consensus sequence of vaccine strain-derived measles virus accrues a remarkably small number of mutations throughout the nonsegmented negative-stranded RNA genome. Interestingly, we detected a nonrandom distribution of genetic alterations within the genome, with an overall decreasing frequency of mutations from the 3' genome start to its 5' end. Comparing the serially passaged viruses to the parental virus on producer cells, we found that the acquired consensus mutations did not drastically change viral replication kinetics or cytolytic potency. Collectively, our data corroborate the genomic stability and excellent safety profile of oncolytic measles virus, thus supporting its continued development and clinical translation as a promising viro-immunotherapeutic.
    MeSH term(s) Animals ; Cell Line, Tumor ; Cell Survival ; Chlorocebus aethiops ; Genomic Instability ; Humans ; Measles virus/genetics ; Measles virus/growth & development ; Mutation ; Oncolytic Virotherapy ; Quasispecies/genetics ; Serial Passage ; Vero Cells ; Virulence/genetics
    Language English
    Publishing date 2020-02-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 219316-4
    ISSN 1465-2099 ; 0022-1317
    ISSN (online) 1465-2099
    ISSN 0022-1317
    DOI 10.1099/jgv.0.001395
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 610: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article: Molecular principles of cancer invasion and metastasis (review).

    Leber, Mathias Felix / Efferth, Thomas

    International journal of oncology

    2009  Volume 34, Issue 4, Page(s) 881–895

    Abstract: The main threat and the reason for most cancer deaths are not the primary neoplasias, but secondary tumors, the metastases. Drastic phenotypic and biochemical changes occur during the metamorphosis of a normal tissue cell into an invasive cancer cell. ... ...

    Abstract The main threat and the reason for most cancer deaths are not the primary neoplasias, but secondary tumors, the metastases. Drastic phenotypic and biochemical changes occur during the metamorphosis of a normal tissue cell into an invasive cancer cell. These alterations concern various areas such as growth factor signaling, cell-cell adhesion, gene expression, motility or cell shape. Cancer cells of epithelial origin can even shed their typical qualities and characteristics and adopt a mesenchymal-like phenotype. This is often referred to as an epithelial-mesenchymal transition. Various oncogenes, tumor suppressor genes and metastasis suppressor genes are known to affect the invasiveness and the metastatic potential of tumor cells. Cells of the innate and adaptive immunity, adjacent stroma cells as well as chemokines and their receptors also play a vital role in the spread of cancer cells. Furthermore, the micro-environment, vascularization and the supply with special cytokines affect the above-mentioned changes. Finally, some researchers claim that tumors consist of two types of cells - transit amplifying cells and cancer stem cells. Only the latter are thought to be able to proliferate indefinitely and thus they might be the cells that successfully spread and initially build most of the clinically relevant metastases. This review article describes some of the molecular principles which underlie those changes as well as covers some aspects of current research.
    MeSH term(s) Cell Adhesion ; Cell Movement ; Cell Proliferation ; Cell Shape ; Cell Transformation, Neoplastic/genetics ; Cytokines/metabolism ; Gene Expression Regulation, Neoplastic ; Genes, Tumor Suppressor ; Humans ; Models, Biological ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasms/genetics ; Neoplasms/pathology ; Signal Transduction
    Chemical Substances Cytokines
    Language English
    Publishing date 2009-03-12
    Publishing country Greece
    Document type Journal Article ; Review
    ZDB-ID 1154403-x
    ISSN 1019-6439
    ISSN 1019-6439
    DOI 10.3892/ijo_00000214
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3690: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article: Enhanced Control of Oncolytic Measles Virus Using MicroRNA Target Sites.

    Leber, Mathias Felix / Baertsch, Marc-Andrea / Anker, Sophie Caroline / Henkel, Luisa / Singh, Hans Martin / Bossow, Sascha / Engeland, Christine E / Barkley, Russell / Hoyler, Birgit / Albert, Jessica / Springfeld, Christoph / Jäger, Dirk / von Kalle, Christof / Ungerechts, Guy

    Molecular therapy oncolytics

    2018  Volume 9, Page(s) 30–40

    Abstract: Measles viruses derived from the live-attenuated Edmonton-B vaccine lineage are currently investigated as novel anti-cancer therapeutics. In this context, tumor specificity and oncolytic potency are key determinants of the therapeutic index. Here, we ... ...

    Abstract Measles viruses derived from the live-attenuated Edmonton-B vaccine lineage are currently investigated as novel anti-cancer therapeutics. In this context, tumor specificity and oncolytic potency are key determinants of the therapeutic index. Here, we describe a systematic and comprehensive analysis of a recently developed post-entry targeting strategy based on the incorporation of microRNA target sites (miRTS) into the measles virus genome. We have established viruses with target sites for different microRNA species in the 3' untranslated regions of either the
    Language English
    Publishing date 2018-04-12
    Publishing country United States
    Document type Journal Article
    ISSN 2372-7705
    ISSN 2372-7705
    DOI 10.1016/j.omto.2018.04.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Cytokine release syndrome-like serum responses after COVID-19 vaccination are frequent but clinically inapparent in cancer patients under immune checkpoint therapy

    Walle, Thomas / Bajaj, Sunanjay / Kraske, Joscha A / Roesner, Thomas / Cussigh, Christiane Sophie / Kaelber, Katharina Anna / Mueller, Lisa Jasmin / Strobel, Sophia Boyoung / Burghaus, Jana / Kallenberger, Stefan / Stein-Thoeringer, Christoph / Jenzer, Maximilian / Schubert, Antonia / Kahle, Steffen / Williams, Anja / Hoyler, Birgit / Zielske, Lin / Skatula, Renate / Sawall, Stefanie /
    Leber, Mathias Felix / Kunes, Russell Z / Krisam, Johannes / Fremd, Carlo / Schneeweiss, Andreas / Krauss, Juergen / Berger, Anne Katrin / Haag, Georg Martin / Zschaebitz, Stefanie / Halama, Niels / Springfeld, Christoph / Kirsten, Romy / Hassel, Jessica C / Jaeger, Dirk / NCT ANTICIPATE Investigators / Ungerechts, Guy

    medRxiv

    Abstract: Cancer patients frequently receive immune checkpoint therapies (ICT) which may modulate immune responses to COVID-19 vaccines. Recently, a cytokine release syndrome (CRS) was observed in a cancer patient who received the BTN162b2 vaccine under ICT. Here, ...

    Abstract Cancer patients frequently receive immune checkpoint therapies (ICT) which may modulate immune responses to COVID-19 vaccines. Recently, a cytokine release syndrome (CRS) was observed in a cancer patient who received the BTN162b2 vaccine under ICT. Here, we analyzed adverse events (AEs) in patients of various solid tumor types undergoing (n=64) or not undergoing (n=26) COVID-19 vaccination under ICT as an exploratory endpoint of a prospectively planned cohort study. We did not observe clinically relevant CRS after vaccination (95% CI [0,0.056]). Short term (<4 weeks) serious AEs were rare (12.5%) and overall AEs under ICT were comparable to unvaccinated patients. Despite the absence of CRS symptoms, we observed a pairwise-correlated set of CRS-associated cytokines upregulated in 42% of patients after vaccination and ICT (>1.5fold). Hence, clinically meaningful CRS appears to be rare in cancer patients under ICT and elevated serum cytokine levels are common but not sufficient to establish CRS diagnosis.
    Keywords covid19
    Language English
    Publishing date 2021-12-11
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.12.08.21267430
    Database COVID19

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  6. Article: Virotherapy in Germany—Recent Activities in Virus Engineering, Preclinical Development, and Clinical Studies

    Nettelbeck, Dirk M. / Leber, Mathias Felix / Altomonte, Jennifer / Angelova, Assia / Beil, Julia / Delic, Maike / Eberle, Jürgen / Ehrhardt, Anja / Engeland, Christine E. / Fechner, Henry / Geletneky, Karsten / Holm, Per Sonne / Kochanek, Stefan / Krutzke, Lea / Kühnel, Florian / Lang, Karl Sebastian / Marchini, Antonio / Moehler, Markus / Muehlebach, Michael /
    Naumann, Ulrike / Nawroth, Roman / Nüesch, Jürg P.F. / Rommelaere, Jean / Lauer, Ulrich Manfred / Ungerechts, Guy

    Viruses, 13(8):1420

    2021  

    Abstract: Virotherapy research involves the development, exploration, and application of oncolytic viruses that combine direct killing of cancer cells by viral infection, replication, and spread (oncolysis) with indirect killing by induction of anti-tumor immune ... ...

    Institution Paul-Ehrlich-Institut
    Abstract Virotherapy research involves the development, exploration, and application of oncolytic viruses that combine direct killing of cancer cells by viral infection, replication, and spread (oncolysis) with indirect killing by induction of anti-tumor immune responses. Oncolytic viruses can also be engineered to genetically deliver therapeutic proteins for direct or indirect cancer cell killing. In this review—as part of the special edition on “State-of-the-Art Viral Vector Gene Therapy in Germany”—the German community of virotherapists provides an overview of their recent research activities that cover endeavors from screening and engineering viruses as oncolytic cancer therapeutics to their clinical translation in investigator-initiated and sponsored multi-center trials. Preclinical research explores multiple viral platforms, including new isolates, serotypes, or fitness mutants, and pursues unique approaches to engineer them towards increased safety, shielded or targeted delivery, selective or enhanced replication, improved immune activation, delivery of therapeutic proteins or RNA, and redirecting antiviral immunity for cancer cell killing. Moreover, several oncolytic virus-based combination therapies are under investigation. Clinical trials in Germany explore the safety and potency of virotherapeutics based on parvo-, vaccinia, herpes, measles, reo-, adeno-, vesicular stomatitis, and coxsackie viruses, including viruses encoding therapeutic proteins or combinations with immune checkpoint inhibitors. These research advances represent exciting vantage points for future endeavors of the German virotherapy community collectively aimed at the implementation of effective virotherapeutics in clinical oncology.
    Keywords combination therapy ; immunotherapy ; virus engineering ; virotherapy ; oncolytic virus ; research in Germany ; Virustherapie ; clinical trials ; therapeutic transgene ; virus targeting
    Language English
    Document type Article
    Database Repository for Life Sciences

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