Potentiating immunotherapy in "immune-cold" solid tumors through orchestrating T cell immunity via tumor-specific genetic engineering.

ABSTRACT: We engineer a tumor-targeted genetic plasmid vector (P_αCD3&LIGHT) to systematically modulate T cell immunity. The tumor-specific telomerase reverse transcriptase (TERT) promoter drives simultaneous expression of tumor necrosis factor superfamily member 14 (LIGHT) and membrane-anchored anti-CD3 single-chain variable fragment (αCD3), which are important immunomodulators with closely clinical relevance. Secreted LIGHT induces high endothelial venule formation and chemokine secretion to recruit circulating lymphocytes, while remodeling extracellular matrix to facilitate immune cell penetration into tumor parenchyma. αCD3 establishes artificial immunological synapses between tumor cells and T lymphocytes. This dual mechanism synergistically establishes tertiary lymphoid structures de

SUBMITTER: He J 

PROVIDER: S-EPMC12765953 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature