Engineering armored CAR‑T cells to overcome the solid tumor microenvironment

CAR‑T cell therapies have achieved remarkable outcomes in hematologic malignancies, yet solid tumors remain a formidable challenge due to target antigen heterogeneity, poor T cell infiltration, and an immunosuppressive tumor microenvironment. This article explores next‑generation armored CAR‑T cell strategies developed in the Priceman laboratory, including the use of membrane‑tethered and fusion‑format IL‑12 to overcome macrophage‑mediated suppression via a programmed death‑ligand 1 (PD‑L1)–IL‑12 fusion protein, approaches to address antigen escape in tumor‑associated glycoprotein‑72 (TAG72)-targeted ovarian cancer therapy, and the application of oncolytic viruses as a universal antigen delivery platform for combinatorial solid tumor targeting.