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EPHB4-Targeted CAR-T Cells Demonstrate Antitumor Activity in an Orthotopic Tongue PDX Model of Oral Squamous Cell Carcinoma

Year: 2026

Type: article

Abstract: Oral squamous cell carcinoma (OSCC) remains associated with poor outcomes and functional impairment despite multimodal treatment, underscoring the need for effective and less invasive therapeutic strategies. Ephrin type-B receptor 4 (EPHB4) is frequently expressed on OSCC cells and represents a potential target for chimeric antigen receptor (CAR)-T cell therapy. In this study, we evaluated the antitumor activity of EPHB4-targeted CAR-T cells (131CAR) using in vitro cytotoxicity assays against the OSCC cell line HSC-4 and an orthotopic tongue patient-derived xenograft (PDX) model established from an OSCC tumor (OC-15) in NOD scid gamma (NSG) mice. Flow cytometry confirmed EPHB4 expression in HSC-4 cells (~90%) and OC-15-derived tumor cells (~68%). In vitro assays demonstrated effector-to-target-ratio-dependent cytotoxicity of 131CAR against HSC-4 cells. In the main in vivo experiment, intratumoral administration of 131CAR suppressed tumor growth and significantly reduced the cytokeratin-defined carcinoma area compared with control groups. Digital pathology further showed a reduced proportion of EPHB4-positive area within the residual carcinoma and increased accumulation of human CD8+ cells in 131CAR-treated tumors. These findings indicate that EPHB4-targeted CAR-T cells exert antitumor activity in an orthotopic OSCC model and support further preclinical evaluation of this therapeutic approach in anatomically relevant settings.

Source: Current Issues in Molecular Biology

DOI: 10.3390/cimb48111115