WEHI Wednesday Seminar hosted by Professor Shalin Naik
 

Dr Cindy Audiger
Research Officer – Naik Laboratory, Immunology division, WEHI

DC1s: emergency recruitment and cancer immunotherapy

 

Davis Auditorium

Join via SLIDO enter code #WEHIWednesday

Including Q&A session
 

Dendritic cells (DCs) are the sentinels of the immune system, constantly patrolling the body and alerting T cells to infections or cancer. Among DC subsets, type 1 conventional DCs (DC1s) – discovered at WEHI in 1992 – are particularly powerful in driving CD8⁺ T cell responses crucial for anti-tumour immunity. Despite their importance, DC1s are exceptionally rare and short-lived.

Efforts to harness DC1s for therapy have followed two main strategies: stimulating “emergency” DCpoiesis, a process that boosts DC production via the growth factor Flt3 ligand (Flt3L) or generating DCs ex vivo in Flt3L supplemented cultures. We have explored both approaches.

First, in mice we examined how Flt3L mobilises DC production and uncovered a previously unrecognised population that arise during “emergency” DCpoiesis, which we term emergency DC1s (eDC1s). These eDC1s exhibit previously unrecognised hybrid properties: they are reminiscent of both haematopoietic progenitors (they divide and are cKit⁺Sca1⁺), and DC1s (they are XCR1⁺, MHC-II⁺ and cross-present antigen to CD8⁺ T cells). Compared to canonical DC1s, these features endow eDC1s with the unique ability to ‘amplify’ immune responses, with implications for cancer immunotherapy.

Second, although recombinant Flt3L can expand DCs in vivo, very recent safety concerns have limited its clinical use, underscoring the need for safer ways to exploit DC1 biology. Despite decades of promise, DC-based cellular immunotherapies have had limited success, largely because most trials used monocyte-derived DCs, which are not bona fide DCs, and because of the lack of scalable methods to produce DC1s, which are predicted to drive anti-tumour immunity.

We have now developed a proprietary Good Manufacturing Process (GMP)-compliant protocol that yields up to 1 billion human cDC1s at >70% purity from a single bag of G-CSF–mobilized blood from patients or donors – far exceeding numbers achievable through leukapheresis. These DC1s are fully functional, capable of cytokine secretion and T cell activation. Supported by a recent MRFF Frontiers grant with academic and translation partners across Australia, we are advancing DC1 immunotherapy for solid cancers, with a clinical trial planned within 3-5 years.

All welcome!