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iRGD + interleukin-2 is an experimental combination immunotherapy designed to treat fibrotic solid tumors, such as pancreatic ductal adenocarcinoma (PDAC) and breast cancer. The combination utilizes iRGD, a tumor-penetrating peptide, to selectively deliver and concentrate low-dose interleukin-2 (IL-2) within the tumor microenvironment. iRGD works by binding to alpha-v integrins and neuropilin-1 (NRP-1) to trigger a transcytotic transport pathway, bypassing the dense desmoplastic stroma that typically limits drug penetration in these cancers. By localizing IL-2, the therapy aims to activate resident cytotoxic CD8+ T cells and reprogram the immunosuppressive environment without inducing the severe systemic toxicities, such as capillary leak syndrome, associated with high-dose IL-2 therapy. Research led by the Sanford Burnham Prebys Medical Discovery Institute has demonstrated that this approach can significantly improve anti-tumor responses and prolong survival in preclinical models.
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