Stroma-Targeted Immunogene Therapy in Pancreatic Cancer 基質標靶免疫基因療法：突破胰臟癌的防護牆

Pancreatic cancer is one of the most difficult cancers to treat because it is surrounded by a dense fibrotic barrier that blocks drugs and immune cells from reaching the tumor. To address this challenge, we developed a stroma-targeted immunogene therapy specifically for pancreatic cancer. Instead of delivering immune proteins directly, we use a smart nanoparticle to carry a gene encoding the immune-stimulating cytokine IL-2 into the tumor microenvironment. This allows cells within the tumor stroma to temporarily produce IL-2 locally, turning the tumor surroundings into small “immune factories.” As a result, more cancer-killing T cells are activated and recruited into the tumor, enhancing the effectiveness of immunotherapy while minimizing systemic side effects. Our goal is to convert immune-resistant pancreatic tumors into immune-responsive ones by reprogramming their own protective barrier.

胰臟癌之所以難以治療，是因為腫瘤外圍有一層厚厚的纖維化「防護牆」，讓藥物和免疫細胞很難進入腫瘤。我們開發了一種專門針對腫瘤間質的免疫基因療法，利用奈米基因載體把能刺激免疫反應的 IL-2 基因送進腫瘤微環境。相較於直接注射激素，我們讓腫瘤周圍的纖維細胞暫時變成「小型免疫工廠」，在局部製造 IL-2，喚醒更多 T 細胞進入腫瘤。這種策略不但提升免疫治療效果，也能減少全身副作用。我們希望能將原本保護癌細胞的屏障，轉變成啟動抗癌免疫的力量。

Stroma-Targeted Gene Delivery for Efficient Immunogene Therapy against Pancreatic Cancer. Mol Ther 1525-0016(25)00813-5.