395P Synthetic IL-12 immunotherapy reverses immune suppression and halts metastasis in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers, characterised by early metastasis, therapeutic resistance, profound cachexia, and an immunosuppressive microenvironment. A defining feature of PDAC is its dense desmoplastic stroma, which restricts immune infiltration and drug delivery. Although cytokine-based immunotherapies such as interleukin-12 (IL-12) show potential, their clinical application has been limited by systemic toxicity. To overcome these barriers, we engineered collagen-binding domain (CBD)-fused IL-12 and IL-7 to localise cytokine activity within the collagen-rich tumour stroma, thereby remodelling the tumour microenvironment (TME) and reducing the toxicity.