Poster Presentation 27th Lorne Cancer Conference 2015

Targeting the Nuclear Transcription Factor MYB using a Novel DNA Vaccine Combined with anti-PD-1 immune Checkpoint Therapy (#142)

Ryan S Cross 1 , Alex J Davenport 1 , Sandra Carpinteri 1 , A/Prof. Robin L Anderson 1 , A/Prof. Phil Darcy 1 , Prof. Rob G Ramsay 1
  1. Peter MacCallum Cancer Centre, Melbourne East, VIC, Australia

Immunotherapy in cancer is being rapidly adopted in the clinic following successes in the treatment of metastatic melanoma. Immune checkpoint blockade is most effective when there are infiltrating CD8 T lymphocytes (TILs). Furthermore, analysis of colorectal cancer patients for TILs has shown that they are more prognostic that standard TNM staging 1; with high TILs being associated with best outcome. MYB is a DNA binding transcription factor that is often over expressed in colorectal cancer 2. The level of MYB expression is also predictive of poor patient outcome, with increased levels seen in secondary metastases compared to primary tumours 2. Thus, MYB is a potential therapeutic target. To target MYB we have developed a novel DNA vaccine. The MYB DNA vaccine contains the sequences for two immunodominant CD4 restricted tetanus epitopes (P2 and P30) at the C and N terminus 3. The MYB DNA vaccine has been shown to be effective in a prophylactic vaccination setting in both the MC38:C57/Bl6 and CT26:BALB/c colorectal cancer mouse models. In this study we have advanced the MYB DNA vaccine to a therapeutic setting. We found that early vaccination, 2 days post inoculation of the MC38 cells, to significantly suppress tumour outgrowth, long term. However, when mice were vaccinated 5 days post inoculation efficacy was lost. The combination of MYB DNA vaccination with anti-PD-1 therapy was able to re-establish efficacy long term, with 50% of tumour outgrowths inhibited. These data indicate that the MYB DNA vaccine, in conjunction with immune checkpoint inhibition, may be an effective immunotherapy for use in patients with colorectal cancer. 

  1. Tosolini, M. et al. Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer research 71, 1263-1271, doi:10.1158/0008-5472.CAN-10-2907 (2011).
  2. Ramsay, R. G. & Gonda, T. J. MYB function in normal and cancer cells. Nature reviews. Cancer 8, 523-534, doi:10.1038/nrc2439 (2008).
  3. Williams, B. B. et al. Induction of T cell-mediated immunity using a c-Myb DNA vaccine in a mouse model of colon cancer. Cancer immunology, immunotherapy : CII 57, 1635-1645, doi:10.1007/s00262-008-0497-2 (2008).