Oral Presentation Joint 2016 COSA and ANZBCTG Annual Scientific Meeting

Immunotherapy - The future (#32)

Ken O'Byrne 1
  1. QUT, Brisbane, QLD, Australia

One of the principal characteristics of malignancy is the suppression of cell-mediated immunity on a background of chronic immune activation that facilitates growth and metastatic spread of the disease. As such there is an imbalance between stimulatory and inhibitory signals regulating the immune response to cancer. These signaling factors include the so-called inhibitory immune checkpoint proteins that modulate the extent and duration of the immune response. This contributes to immune resistance, especially against tumor antigen-specific T-cells, and may be activated by the tumour cells themselves. Targeting these checkpoints is a novel approach to cancer immunotherapy. Current immunotherapy focuses on the programmed cell death protein 1 receptor (PD-1) and its ligands (PD-L1, PD-L2), and on the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Specific anti-PD-1 and anti-PDL-1 antibodies have been developed that block the ligand-receptor interaction. This facilitates recognition of neo-antigens presented by cancer cells by immune effector tumor-infiltrating T-cells. CTLA-4 inhibitors such as ipilimumab and tremelimumab have also been developed. All of these checkpoint inhibitors have single agent activity in a broad range of tumours. Of significant interest in current clinical studies is the combination of PD-1, PD-L1 and CTLA-4 inhibitors that have resulted in dramatic response rates in melanoma and non-small cell lung cancer. Other novel approaches include combining checkpoint inhibitors with chemotherapy, oncogene targeted therapies, vaccines and other immune agents such as those targeting GITR, adenosine and OX-40. Finally activation of Natural Killer cells, part of our innate immune response, and ‘eat-me’ signalling in macrophages may also prove to be effective immune strategies in the future.