Poster Presentation 29th Lorne Cancer Conference 2017

Advancing a Myb DNA vaccine in the context of myb-dependent hematopoietic malignancies (#257)

Sara Roth 1 , Shienny Sampurno 1 , Michaela Waibel 1 , Sandra Carpinteri 1 2 , Rosemary Millen 1 , Lloyd Pereira 1 , Jordane Malaterre 1 , Joseph Kong 1 , Glen Guerra 1 , Paul Neeson 1 , Ricky Johnstone 1 , Ryan Cross 2 , Alexander Heriot 1 , Jayesh Desai 1 3 , Robert G. Ramsay 1
  1. Peter MacCallum Cancer Centre, Melbourne, VICTORIA, Australia
  2. Walter and Eliza Hall Institute for Medical Research, Melbourne, Victoria, Australia
  3. Royal Melbourne Hospital, Melbourne, Victoria, Australia

Subheadings: Therapeutic MYB vaccination in the setting of MYB-dependent blood cancer

Aims: To test the efficacy of a MYB vaccine in the controlling hematopoietic malignancies.

Background: DNA vaccines are currently used as a treatment for infectious diseases as well as cancer and present an affordable alternative to other immune related therapies currently under development. Our lab has developed a DNA vaccine encoding a fusion protein of Myb proto-oncogene flanked by two tetanus toxoid peptides, which has shown therapeutic protection in preclinical models of colorectal cancer (1,2) and is now heading for the first in-man clinical trial.

However, colorectal cancer is not the only cancer with a dependency and high expression of the transcription factor MYB. Hence, the application of our DNA vaccine may also be beneficial for treatment of other cancers. In our latest study we analysed leukemia and lymphoma models.

Methods: EmMyc lymphoma or Tel-Jak2 leukemia-prone mice were crossed onto a c-Mybplt4/plt4 hypomorphic mutant mouse background and tracked over time to assess disease progression. As the Tel-Jak2 but not the EmMyc model showed a MYB-dependency we then inoculated cohorts of mice with Tel-Jak2 leukemic cells in the context of MYB-vaccination. Clinical and hematopoietic parameters were then evaluated. Other immunomodulatory approaches were also employed in combination with the MYB vaccine.

Results: Tel-Jak2 leukemia-prone mice showed significantly delayed progression on a hypomorphic mutant background due to compromised leukemia development suggesting that this model is MYB-dependent. MYB has been shown to be central to stem/progenitor cell self-renewal; a property also required for malignant blood cells(3). The Tel-Jak2 leukemia cells also showed elevated Bcl-2 gene expression consistent with it being transcriptionally regulated by MYB. At the time of cull the vaccinated mice had smaller spleens and lower overall white blood cell counts.

Conclusions: The MYB DNA vaccine may have utility in the management of malignancies beyond solid tumours, such as leukemia.

  1. 1. Cross, R.S., Malaterre, J., Davenport, A.J., Carpinteri, S., Anderson, R.L., Darcy, P.K. and Ramsay, R.G. (2015) Therapeutic DNA vaccination against colorectal cancer by targeting the MYB oncoprotein. Clinical & Translational Immunology 4: e30.
  2. 2. Carpinteri, S., Williams, B.B., Miao, Yu. R., Cullinane, C., Malaterre, J., Norris, M.D., Haber, M., Anderson, R., Darcy. P.K. and Ramsay, R.G. (2012) Optimizing DNA vaccines against Nuclear Oncogenes. Immuno-Gastroenterology 1(2): 108-118.
  3. 3. Ramsay, R.G. (2005) c-Myb a stem-progenitor cell regulator in multiple tissue compartments. Growth Factors. 23: 253-261.