37P Synthetic tumour-infiltrating interleukin (IL)-12 for targeted and tolerable immunotherapy reduces metastasis in pancreatic cancer

Abstract

Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) is a root cause of lethality in patients. The metastasis is promoted by abundant proteases in the PDAC microenvironment. Synthetic immuno-oncology opens new avenues towards overcoming limitations of standard immunotherapy agents, previously unsuccessful in PDAC. Anti-tumour cytokines such as IL-12 poorly infiltrate the stroma of solid tumours and trigger toxicity. Here, by exploiting the abundant proteases in PDACs, a targeted and tolerable masked Collagen-Binding Domain CBD-Il12 (mCBD-Il12) was produced by fusing the mask to the p35 subunit of Il-12 through a cleavable linker.