Clec9A targeting antibodies as a new immunotherapy for prostate cancer

  • Radford, Kristen (Primary Chief Investigator (PCI))
  • Lahoud, Mireille (Chief Investigator (CI))

Project: Research

Project Description

Dendritic cells (DC) play a pivotal role in the initiation and regulation of immune responses, including the induction of cytotoxic T lymphocyte (CTL) responses. CTL are essential for the eradication of cancers and many pathogens for which there are currently no effective vaccines 1-3**. We pioneered the discovery of the human CD141+ DC subtype that are widely considered to be the most clinically relevant human DC subset for initiating CTL responses and are therefore prime targets for vaccines 4**. We also discovered the C-type lectin (CLR) like receptor, CLEC9A, that is specifically expressed by CD141+ DC 5**. We propose that anti-CLEC9A antibodies (Ab) can be used to deliver therapeutic payload antigen (Ag) directly to CD141+ DC in vivo and exploited as a new vaccine for metastatic prostate cancer to induce potent CTL and CD4+ T cell responses. We have already demonstrated proof-of-concept of this approach in mouse models 5-7** and now aim to translate this platform to humans. We have developed a novel human chimeric Ab specific to human CLEC9A that is genetically fused to a model human viral Ag. In parallel, we developed a novel humanized mouse model engineered to generate physiologically relevant human CD141+ DC 8**, providing an ideal test bed for comprehensive evaluation of next generation CD141+ DC targeting vaccines. The overall aim of this research proposal is to combine these new technologies for an integrated, preclinical evaluation of novel anti-human CLEC9A Ab and compare their ability to induce CTL responses with DEC-205 Ab targeting, which targets all human DC subsets and is currently in clinical trials (CellDex Therapeutics).
StatusNot started

Keywords

  • Dendritic cell
  • Cell surface receptors
  • Immune modulation
  • Cancer immunotherapy