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**4H1128ζ-IL12 is a second-generation armored chimeric antigen receptor (CAR) T cell therapy engineered to target the tumor-associated antigen Muc16 (also known as CA125), with additional genetic modification to constitutively secrete interleukin-12 (IL-12).** These CAR T cells are designed to increase antitumor efficacy by both direct cytotoxicity against Muc16-expressing ovarian cancer cells and by modulating the tumor microenvironment. IL-12 secretion augments T cell effector functions, reduces T cell exhaustion, and has immunomodulatory effects, including boosting pro-inflammatory cytokine production and depleting immunosuppressive tumor-associated macrophages through the Fas/FasL pathway. Preclinical studies have shown enhanced tumor cytolysis and survival benefit in mouse models, as well as altered gene expression toward a more inflammatory, less exhausted T cell phenotype[1][2].
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