Molecular Horizons Seminar - Professor Kristen Radford

Therapeutic vaccines are the next frontier of cancer immunotherapy and offer enormous potential to improve outcomes for cancer patients. Vaccines aim to induce tumour regression and prevent recurrence whilst avoiding adverse reactions by establishing long lasting anti-tumour immune memory. Dendritic cells (DCs) are uniquely capable of initiating cytotoxic CD8+ T cell immune responses to cancer and are required for vaccine efficacy.  Monocyte-derived DC (MoDC) administered as vaccines have proven to be safe and effective at inducing tumour immune responses in hundreds of cancer patients but have had limited clinical benefit. We characterized a rare population of human DCs known as CD141+ DC or cDC1 and demonstrated their superiority to other human DC subtypes at cross-presenting dead cell antigen to CD8+ T cells.  We developed innovative models to grow large numbers of functional human cDC1 from cord blood progenitors in vitro and in humanized mice in vivo. We have shown that human cDC1 can be effectively harnessed as novel vaccines either by targeting antigen to them directly in vivo (via their exclusive expression of CLEC9A) or as adoptively transferred cellular therapeutics, providing a strong rationale to exploit human DC1 as next generation cancer vaccines.