Dendritic cells (DCs) are key regulators of the immune system and have long been explored for cancer immunotherapy due to their ability to adapt to evolving tumors. They continuously capture, process, and present tumor antigens to T cells, driving cancer cell elimination. To date, immunotherapy efforts have focused on monocyte-derived DCs (MoDCs), but despite numerous clinical trials, only Provenge® has received FDA approval although not widely used.
Extensive evidence suggests that type 1 conventional DCs (DC1s) are a superior alternative. However, few DC1-based therapy has reached clinical trials due to three major challenges: (1) their scarcity, (2) the lack of a GMP-compliant manufacturing protocol, and (3) difficulties in their delivery and activation within tumors. Overcoming these barriers could unlock the full potential of DC1s in cancer treatment.
Leveraging prior knowledge of DC1 development with regards to the importance of Notch signalling and transcription factor usage, we have now developed an animal-derived ingredient free proprietary GMP-compliant protocol that yields up to 1 billion human DC1s at >70% purity from a single bag of G-CSF-mobilized blood (for autologous DC1 immunotherapy) - far exceeding numbers achievable through leukapheresis (1-20 million). Alternatively, 1 billion can at >90% purity can be achieved from a single cord blood donation an off-the-shelf allogeneic DC1 therapy. Importantly, DC1s are fully functional, capable of cytokine secretion and T cell activation, offering a powerful platform for next-generation DC-based immunotherapies. Our process therefore generates sufficient DC1 numbers equivalent to past MoDC trials to test their efficacy in a patient setting.
We are now advancing toward clinical translation with a Phase 1 clinical trial planned within the next five years, aiming to establish next-generation DC1-based immunotherapy as a viable treatment for solid cancer.