Poster Presentation Melbourne Immunotherapy Spring Symposium 2025

Next-generation dendritic cell immunotherapy for intractable solid cancers (#120)

Devi Jenika 1 , Chengyu Lin 1 , Patrick Constantinescu 2 , Jessica Li 2 , Jane Oliaro 2 , Cindy Audiger 1 , Shalin Naik 1
  1. Immunology Division, Walter and Eliza Hall Institute, Parkville, VIC, Australia
  2. Centre of Excellence in Cellular Immunotherapy, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

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.

Recent evidence suggests that type 1 conventional DCs (DC1s) are a superior alternative. However, no 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.

We have developed a novel protocol that dramatically improves DC1 yield compared to existing GMP-like methods, increasing purity from 5% to 50% and generating up to 50 times more DC1s. This protocol produces functional DC1s from both healthy donors and cancer patients, as confirmed by cytokine production and T cell activation assays. Our approach is projected to generate 800 million DC1s from a single bag of G-CSF-mobilized blood - ten times more than the only published GMP-compliant protocol.

We are now advancing toward clinical translation with WILDCARD, a Phase 1 clinical trial planned within the next five years, aiming to establish DC1-based immunotherapy as a viable treatment for cancer.