Adenovirus Is an Optimal Vector for Cancer Immunotherapy

There are several reasons why adenovirus is an optimal vector for cancer immunotherapy:

  1. Adenovirus can both prime and boost immune responses1
    • Adenovirus primarily activates CD8+ T cells (via TLR 9 and via TLR independent mechanisms) → optimal for cancer immunotherapy
  2. Vaccinia is less effective in priming T cell responses than adenovirus2
  3. Herpes simplex virus (HSV) may not be optimal for cancer immunotherapy:
    • HSV has evolved multiple immune evasion strategies including inhibition of T cell responses3,5
    • Neurotropism may pose safety concerns
    • TLR activation profile not optimal (TLR 2 and 4)4
  4. Ease of constructing and manufacturing new adenovirus vectors
    • Vaccinia: large genome, genomic repeats, four distinctive forms of infectious particles complicates cloning and QC
    • HSV: large genome, multiple deletions needed for safety -> complex
    • Vaccinia and HSV: enveloped viruses -> risk of host derived contaminants
    • RNA viruses: genomic instability -> challenge for accommodation of transgenes

References

  1. Draper and Heeney 2010 Nat Rev Microbiol
  2. Bart et al 2014 J Clin Invest
  3. Raftery et al 1999 J Exp Med
  4. Villalba et al 2012 Med Microbiol Immunol 5.Barcy et al 2001 J Immunol
  5. Barcy et al 2001 J Immunol