Improved system for producing adenoviral vectors

Information

  • Research Project
  • 7405800
  • ApplicationId
    7405800
  • Core Project Number
    R43CA132468
  • Full Project Number
    1R43CA132468-01
  • Serial Number
    132468
  • FOA Number
    PA-06-13
  • Sub Project Id
  • Project Start Date
    9/21/2007 - 17 years ago
  • Project End Date
    8/31/2009 - 15 years ago
  • Program Officer Name
    PARK, EUN-CHUNG
  • Budget Start Date
    9/21/2007 - 17 years ago
  • Budget End Date
    8/31/2009 - 15 years ago
  • Fiscal Year
    2007
  • Support Year
    1
  • Suffix
  • Award Notice Date
    9/21/2007 - 17 years ago
Organizations

Improved system for producing adenoviral vectors

First generation non-replicative adenoviral vectors show promise as anti-cancer agents and as[unreadable] prophylactic vaccines. Current methods for manufacturing these vectors use either the 293 cell[unreadable] line or the PER.C6 cell line. These producer cells provide complementary E1a and E1b viral[unreadable] function in the cell for disabled adenoviral vectors. The 293 cell line has been very useful and[unreadable] widely used for making relatively small batches of vector for early stage clinical trials. However the[unreadable] frequency with which it generates replication competent adenovirus, which disqualifies from 10 to[unreadable] 50% of batches depending on the vector, means that, as the manufacturing processes are scaled[unreadable] up in later stage clinical trials, or for marketing, it becomes less and less acceptable. As scale[unreadable] increases, increasing numbers of batches exceed the FDA mandated allowable contamination[unreadable] level of 1RCA/3x10e10 viral particles, and such a manufacturing process cannot be claimed to be[unreadable] ?controlled? by FDA standards if the failure rate is greater than ~ 10%. PER.C6 cells use a[unreadable] specifically designed matched vector to eliminate sequence overlap between producer line and[unreadable] vector. The system is not compatible with most current clinical vectors and is not available to[unreadable] academic researchers or small companies. A modest 10 fold reduction in RCA frequency over[unreadable] that seen in 293 cells would provide a robust production system if the vector productivity were[unreadable] equivalent. We have constructed a cell line named c24 based on the human tumor line A549,[unreadable] which is as productive as 293 cells, is stable, is free of mycoplasma and carries 1-2 copies of an[unreadable] E1 expression plasmid with very limited overlap with conventional adenoviral vectors. We propose[unreadable] to rigorously test the RCA frequency in c24 compared to 293 cells, and to adapt it to serum free[unreadable] growth. If the RCA generation can be reduced by >10-fold, and in a serum free environment, then[unreadable] c24 can provide the basis for a reliable vector production system with a further improved safety[unreadable] profile that can be widely used to manufacture adenoviral vector products, including[unreadable] Advantagene?s own late stage pipeline.

IC Name
NATIONAL CANCER INSTITUTE
  • Activity
    R43
  • Administering IC
    CA
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    213871
  • Sub Project Total Cost
  • ARRA Funded
  • CFDA Code
    393
  • Ed Inst. Type
  • Funding ICs
    NCI:213871\
  • Funding Mechanism
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    ADVANTAGENE, INC
  • Organization Department
  • Organization DUNS
    192959851
  • Organization City
    Auburndale
  • Organization State
    MA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    02466
  • Organization District
    UNITED STATES