Oral Presentation Australasian Extracellular Vesicles Conference 2020

Dancing with the devil: immune strategies to combat Tasmanian Devil Facial Tumour Disease (DFTD) (#13)

Bruce Lyons 1 , Andrew S Flies 1 , Chrissie B Ong 1 , Camila Espejo 1
  1. University of Tasmania, Hobart, TAS, Australia

Since 1996, a transmissible facial tumour (DFTD) is estimated to have reduced the population of wild Tasmanian devils, the largest extant marsupial carnivore, by 80-90%. Efforts to preserve this species include a meta-population of captive devils across many sites throughout Australia and the world, coupled with an extensive and genetically managed captive breeding program. However, survival of the species in the wild to preserve ecological balance is the primary goal.

Our group investigates why this tumour allograft is not rejected immunologically, with the aim of developing a protective vaccine. A key immune evasion strategy used by DFTD is downregulation of MHC-I to avoid graft rejection. We can induce an immune response against DFTD in the most devils using immunisation with interferon-gamma cultured DFTD cells which re-express MHC-I. Parallel immunotherapy studies show it is also possible to trigger tumour rejection in a subset of devils. Furthermore, a small percentage of animals in the wild exhibit tumour regressions, which often coincides with detectable antibody responses against DFTD cells. The astonishing discovery of a second, independently arising facial tumour in the channel area of southern Tasmania has challenged the widely held view that transmissible cancers are rare events.

Our current research efforts include the development of cell free vaccine approaches, using vesicles derived from cultured DFTD cells. These artificially produced vesicles may have significant benefits over whole cell approaches, including removing the likelihood of inadvertent disease transmission by incomplete cell inactivation. Another benefit is that the vesicle size is within the range of many infectious agents, which is thought to be more likely to result in immune recognition and activation. Furthermore, immune activating ligands such as costimulatory molecules can be included in the vesicles to give them antigen presenting properties able to induce cell mediate immunity, which is thought to be required for effective responses against cancer. As the preparations are cell free, this can be achieved without them being classified as GMO’s, which may be beneficial in jurisdictions such as Tasmania which have a moratorium on the use of genetically modified live organisms.