Matches in SemOpenAlex for { <https://semopenalex.org/work/W1656451353> ?p ?o ?g. }
- W1656451353 abstract "Wild-type viruses with intrinsic oncolytic capacity in human includes DNA viruses like some autonomous parvoviruses and many RNA viruses. Recent advances in molecular biology have allowed the design of several genetically modified viruses, such as adenovirus and herpes simplex virus that specifically replicate in, and kill tumor cells. However, still several hurdles regarding clinical limitations and safety issues should be overcome before this mode of therapy can become of clinical relevance. It includes limited virus spread in tumor masses, stability of virus in the blood, trapping within the liver sinusoids, transendothelial transfer, and/or vector diffusion of viral particles to tumor cells, limited tumor transduction, immune-mediated inactivation or destruction of the virus. For replication-competent vectors without approved antiviral agents, suicide genes might be used as fail-safe mechanism. Cancer stem cells are a minor population of tumor cells that possess the stem cell property of self-renewal. Therefore, viruses that target the defective self-renewal pathways in cancer cells might lead to improved outcomes.In this thesis, data we generated in the field of oncolytic autonomous parvoviruses are presented.We replaced capsid genes by reporter genes and assessed expression in different types of human cancer cells and their normal counterparts, either at the level of whole cell population, (CAT ELISA) or at the single cell level, (FACS analysis of Green Fluorescent Protein). Cat expression was substantial (up to 10000 times background) in all infected tumor cells, despite variations according to the cell types. In contrast, no gene expression was detected in similarly infected normal cells, (with the exception of an expression slightly above background in fibroblasts.). FACS analysis of GFP expression revealed that most tumor cells expressed high level of GFP while no GFP positive normal cells could be detected with the exception of very few (less than 0.1%) human fibroblast cells expressing high level of GFP. We also replace capsid genes by genes coding for the costimulatory molecules B7-1 and B7-2 and show that, upon infection with B7 recombinant virions, only tumor cells display the costimulatory molecules and their immunogenicity was increased without any effect on normal cells. Using a recombinant MVM containig the Herpes Simplex thymidine kinase gene, we could get efficient killing of most tumor cell types in the presence of ganciclovir, whithout affecting normal proliferating cells. We also produced tetracycline inducible packaging cell lines in order to improve recombinant vectors yields. The prospects and limitations of these different strategies will be discussed.An overview is given of the general mechanisms and genetic modifications by which oncolytic viruses achieve tumor cell-specific replication and antitumor efficacy. However, as their therapeutic efficacy in clinical trials is still not optimal, strategies are evaluated that could further enhance the oncolytic potential of conditionally replicating viruses in conjunction with other standard therapies. Another exciting new area of research has been the harnessing of naturally tumor-homing cells as carrier cells to deliver oncolytic viruses to tumors. The trafficking of these tumor-homing cells (stem cells, immune cells and cancer cells), which support proliferation of the viruses, is mediated by specific chemokines and cell adhesion molecules and we are just beginning to understand the roles of these molecules. Finally, we will explore some ways deserving further study in order to be able to utilize various oncolytic viruses for effective cancer treatment." @default.
- W1656451353 created "2016-06-24" @default.
- W1656451353 creator A5030350487 @default.
- W1656451353 creator A5066527595 @default.
- W1656451353 date "2008-10-21" @default.
- W1656451353 modified "2023-09-24" @default.
- W1656451353 title "Oncolytic viruses cancer therapy" @default.
- W1656451353 cites W1492631261 @default.
- W1656451353 cites W1637884427 @default.
- W1656451353 cites W1749496846 @default.
- W1656451353 cites W1963483847 @default.
- W1656451353 cites W1967321715 @default.
- W1656451353 cites W1968566356 @default.
- W1656451353 cites W1986523328 @default.
- W1656451353 cites W2001758369 @default.
- W1656451353 cites W2016080258 @default.
- W1656451353 cites W2037596266 @default.
- W1656451353 cites W2037822809 @default.
- W1656451353 cites W2045415534 @default.
- W1656451353 cites W2052175782 @default.
- W1656451353 cites W2057382033 @default.
- W1656451353 cites W2060490849 @default.
- W1656451353 cites W2063512646 @default.
- W1656451353 cites W2064458649 @default.
- W1656451353 cites W2068732162 @default.
- W1656451353 cites W2073134590 @default.
- W1656451353 cites W2088668440 @default.
- W1656451353 cites W2090599158 @default.
- W1656451353 cites W2092414440 @default.
- W1656451353 cites W2093382343 @default.
- W1656451353 cites W2107199882 @default.
- W1656451353 cites W2109517496 @default.
- W1656451353 cites W2115804513 @default.
- W1656451353 cites W2121627265 @default.
- W1656451353 cites W2146549504 @default.
- W1656451353 cites W2249995212 @default.
- W1656451353 hasPublicationYear "2008" @default.
- W1656451353 type Work @default.
- W1656451353 sameAs 1656451353 @default.
- W1656451353 citedByCount "0" @default.
- W1656451353 crossrefType "journal-article" @default.
- W1656451353 hasAuthorship W1656451353A5030350487 @default.
- W1656451353 hasAuthorship W1656451353A5066527595 @default.
- W1656451353 hasConcept C104317684 @default.
- W1656451353 hasConcept C111599444 @default.
- W1656451353 hasConcept C121608353 @default.
- W1656451353 hasConcept C15152581 @default.
- W1656451353 hasConcept C159047783 @default.
- W1656451353 hasConcept C2522874641 @default.
- W1656451353 hasConcept C2781196997 @default.
- W1656451353 hasConcept C2908647359 @default.
- W1656451353 hasConcept C32470452 @default.
- W1656451353 hasConcept C34981463 @default.
- W1656451353 hasConcept C40767141 @default.
- W1656451353 hasConcept C43953973 @default.
- W1656451353 hasConcept C49744831 @default.
- W1656451353 hasConcept C502942594 @default.
- W1656451353 hasConcept C54355233 @default.
- W1656451353 hasConcept C55493867 @default.
- W1656451353 hasConcept C71924100 @default.
- W1656451353 hasConcept C82210918 @default.
- W1656451353 hasConcept C86803240 @default.
- W1656451353 hasConcept C96232424 @default.
- W1656451353 hasConcept C99454951 @default.
- W1656451353 hasConceptScore W1656451353C104317684 @default.
- W1656451353 hasConceptScore W1656451353C111599444 @default.
- W1656451353 hasConceptScore W1656451353C121608353 @default.
- W1656451353 hasConceptScore W1656451353C15152581 @default.
- W1656451353 hasConceptScore W1656451353C159047783 @default.
- W1656451353 hasConceptScore W1656451353C2522874641 @default.
- W1656451353 hasConceptScore W1656451353C2781196997 @default.
- W1656451353 hasConceptScore W1656451353C2908647359 @default.
- W1656451353 hasConceptScore W1656451353C32470452 @default.
- W1656451353 hasConceptScore W1656451353C34981463 @default.
- W1656451353 hasConceptScore W1656451353C40767141 @default.
- W1656451353 hasConceptScore W1656451353C43953973 @default.
- W1656451353 hasConceptScore W1656451353C49744831 @default.
- W1656451353 hasConceptScore W1656451353C502942594 @default.
- W1656451353 hasConceptScore W1656451353C54355233 @default.
- W1656451353 hasConceptScore W1656451353C55493867 @default.
- W1656451353 hasConceptScore W1656451353C71924100 @default.
- W1656451353 hasConceptScore W1656451353C82210918 @default.
- W1656451353 hasConceptScore W1656451353C86803240 @default.
- W1656451353 hasConceptScore W1656451353C96232424 @default.
- W1656451353 hasConceptScore W1656451353C99454951 @default.
- W1656451353 hasLocation W16564513531 @default.
- W1656451353 hasOpenAccess W1656451353 @default.
- W1656451353 hasPrimaryLocation W16564513531 @default.
- W1656451353 hasRelatedWork W1520313218 @default.
- W1656451353 hasRelatedWork W1975406089 @default.
- W1656451353 hasRelatedWork W1985582416 @default.
- W1656451353 hasRelatedWork W1989295263 @default.
- W1656451353 hasRelatedWork W1993515057 @default.
- W1656451353 hasRelatedWork W2014532258 @default.
- W1656451353 hasRelatedWork W2066381638 @default.
- W1656451353 hasRelatedWork W2082364178 @default.
- W1656451353 hasRelatedWork W2092418823 @default.
- W1656451353 hasRelatedWork W2094495139 @default.
- W1656451353 hasRelatedWork W2097026970 @default.
- W1656451353 hasRelatedWork W2411135501 @default.