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Genetic Trick Turns Cold Tumors Hot, Supercharging ImmunotherapyLongevity & Aging

Genetic Trick Turns Cold Tumors Hot, Supercharging Immunotherapy

Researchers engineered a tumor-specific genetic plasmid (PαCD3&LIGHT) delivered via nanoparticles that simultaneously expresses two immune activators—LIGHT and membrane-anchored anti-CD3—exclusively in cancer cells. LIGHT recruits lymphocytes by forming high endothelial venules and dissolving the dense extracellular matrix, while anti-CD3 creates artificial bridges between T cells and tumor cells. Together, they generate tertiary lymphoid structures deep within tumors, sustain stem cell-like CD8+ T cells, and reverse T cell exhaustion. In mouse models of melanoma, colon cancer, and breast cancer, this approach suppressed tumor growth on its own and dramatically improved outcomes when combined with checkpoint inhibitors or CAR-T cell therapy, without obvious systemic toxicity.

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