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ttIL-12 is a tumor-targeted interleukin-12 (IL-12) gene therapy delivered as a plasmid DNA (pDNA) construct. It is engineered to target Cell-Surface Vimentin (CSV), a marker specifically expressed on the surface of tumor cells across various aggressive cancers. By localizing IL-12 expression to the tumor microenvironment, ttIL-12 enhances antitumor immunity while minimizing the systemic toxicity typically associated with recombinant IL-12. The therapy works by promoting the infiltration of non-exhausted CD8+ T cells and increasing the production of interferon-gamma (IFNγ) and the chemokine CXCL9. Simultaneously, it suppresses the recruitment of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) by downregulating chemokines like CCL22 and CXCL2. Preclinical studies have demonstrated its potential in treating aggressive cancers such as breast carcinoma, sarcoma, and osteosarcoma, particularly when combined with surgical resection to suppress metastasis and prolong overall survival.
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