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sdahlseng10

Replication-competent Lentivirus Analysis of Clinical Grade Vector Products - 0 views

www.ncbi.nlm.nih.gov/...PMC3048188

HIV lentivirus vector replication competent gene therapy

shared by sdahlseng10 on 02 Oct 12 - No Cached
  • sdahlseng10 on 02 Oct 12
     
    Supplementary Article to Lesch et al. (2011); journal club 1: This article helps us understand the dangers of attenuated lentiviruses used for gene therapy and other clinical applications. It also details a method for screening newly synthesized lentiviruses for replication competency.
Casey Finnerty

Research - A Neuro-Oncology Laboratory at Northwestern University in Chicago - 1 views

www.lesniaklab.com/research.html

virotherapy

shared by Casey Finnerty on 12 Oct 16 - No Cached
  • Most adenoviruses that have been historically used for gene therapy have been based on serotype 5 (AdWT). Unfortunately, expression of the primary receptor for Ad5 (the coxsackie-adenovirus receptor, CAR) is highly variable on cancer cells. In fact, several studies have demonstrated a resistance of malignant glioma to adenoviral vectors, a finding that was subsequently attributed to the quantitative deficiency of CAR on brain tumor cells.
  • First, we tested a variety of tumor specific promoters and identified survivin (S) as an excellent tumor specific promoter for transcriptional control of E1a, a gene essential for CRAd replication (J Neurosurg 104:583, 2006; Cancer Biol Ther 6:679, 2007).
  • Based on the above date data, we then created a novel oncolytic adenoviral vector which utilizes the survivin promoter and binds to heparan sulfate proteoglycans expressed on malignant brain tumors and named this new vector CRAd-S-pk7 (Hum Gene Ther 18:589, 2007).
    • Casey Finnerty
      Casey Finnerty on 12 Oct 16
       
      How specific is the binding/tropism? HS is fairly widespread throughout the body.
  • ...6 more annotations...
  • Second, we have identified several receptors that are over-expressed on brain tumor cells and created a series of pseudotyped Ad5 vectors that recognize these receptors
  • Our studies with CRAd-S-pk7 indicate that the virus provides the highest level of viral replication and tumor oncolysis in glioma cell lines. At the same time, we observed minimal viral replication and toxicity in normal human brain. Injection of CRAd-S-pk7 inhibited xenograft brain tumor growth by more than 300%.
  • We were the first group in the country to show that human mesenchymal stem cells can be effectively loaded with a replication competent virus and effectively deliver it to an experimental glioma model
  • When oncolytic vectors are loaded onto stem cells, the virus effectively "hides" from the immune system for an extended period of time. The ability of stem cells to suppress the anti-viral immune response in a permissive and tumor-bearing animal model is the subject of one of our latest manuscript
  • Finally, to further enhance the therapeutic efficacy of stem cells, we have optimized them to specifically traffic to intracranial tumors via genetic modification with single-chain antibodies against antigens expressed on gliomas
  • Our latest work in this area supports the development of neural stem cell based cell carriers for oncolytic virotherapy
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