Spatially enforced engagement of PD-1⁺ T cells with AXL⁺ cells reprograms the tumor microenvironment and overcomes anti-PD-1 resistance

A non-tandem tetravalent PD-1/AXL bispecific (BiTE-AXL/PD-1) enhances AXL-dependent PD-1+ T-cell engagement and tumor-cell killing, outperforming anti-AXL plus anti-PD-1 in HNSCC models.

• Why it matters: AXL overexpression promotes immune suppression and anti-PD-1 resistance, and standard antibody combinations do not enforce PD-1+ T-cell proximity to AXL+ tumor cells in the tumor microenvironment.
• What they did: The bispecific was tested in vitro and in humanized and immunocompetent head and neck squamous cell carcinoma models, compared against monospecific anti-AXL plus anti-PD-1, with spatial multiplex imaging in an anti-PD-1-resistant murine model.
• The result: BiTE treatment significantly delayed tumor growth versus the antibody combination and shifted tumors from fibroblast-dominated, exhausted CD8+ T-cell niches to dendritic-cell- and CD8+ T-cell-enriched antitumor niches.