Oral Presentation 6th Australian Health and Medical Research Congress 2012

Activating the Tasmanian devil's Immune Response to Target DFTD (#134)

Gabriella K. Brown 1 , Alexandre Kreiss 1 , A. Bruce Lyons 2 , Gregory M. Woods 3
  1. Menzies Research Institute Tasmania, Hobart, Tasmania, Australia
  2. School of Medicine, University of Tasmania, Hobart, Tasmania, Australia
  3. Menzies Research Institute Tasmania, Hobart, Tasmania, Australia

The Tasmanian devil is under threat of extinction due to the emergence of an aggressive contagious cancer which is transmitted through biting. In the sixteen years since its appearance, Devil Facial Tumour Disease (DFTD) has caused an 80 percent decline in the Tasmanian devil population. The disease is invariably fatal and infects its hosts with no evidence of an immune response. Without intervention the devil may become extinct in the wild within 20 years. The development of a vaccine or immunotherapy for DFTD would provide an option to protect the species. This study aimed to activate Tasmanian devil lymphocytes to target DFTD using mitogen stimulation.

Tasmanian devil peripheral blood mononuclear cells were stimulated with 25µg/ml Concanavalin (Con) A for 48 hours. Chromium release assays were performed against DFTD cells to assess cytotoxicity of the mitogen activated killer (MAK) cells. The technique was used to prepare MAK cells from the blood of a DFTD diseased devil for immunotherapy. The effects of this treatment were analysed using immunohistochemistry for CD3, MHC II and the DFTD marker periaxin.

The activation of devil lymphocytes using Con A stimulation resulted in the generation of highly cytotoxic cells which killed up to 70% of DFTD tumour cells in vitro. A single intratumoural injection of MAK cells as an immunotherapy resulted in increased numbers of CD3+ and MHC II+ immune cells at the DFTD tumour periphery. After two more injections, CD3+ and MHC II+ cells were evident within DFTD tumour regions. Additionally, changes in DFTD cell morphology were observed within the tumour.

The results of this study provided the first evidence for consistent activation of Tasmanian devil lymphocytes to kill DFTD cancer cells. Injection of MAK cells may provide a basis for an immunotherapy against DFTD, and more in vivo trials should urgently be performed.