DaRT & PD-1 Blockade Enhance HNSCC Response

Introduction: DaRT, a novel high-LET radiotherapy using alpha-emitting atoms, shows promise in advanced HNSCC, but recurrence limits efficacy. We investigated combining DaRT with anti-PD-1 to enhance tumor response, hypothesizing PD-1 blockade augments DaRT-induced anti-tumor immunity.

Materials and Methods: Orthotopic 4NQO-induced murine HNSCC models (4NQO-L) with larger initial tumors were used. Mice were treated with DaRT, anti-PD-1, or combination. Tumor volume was measured. Serum samples were collected to assess cytokine levels (e.g., IFN-γ, IL-10) as indicators of systemic immune response.

Results and Discussion: Combined DaRT and anti-PD-1 significantly reduced tumor growth compared to monotherapies. At day 30, the combination group showed a substantial tumor volume reduction. Preliminary data indicates 70 % of mice in the combination group achieved complete tumor regression. Cytokine analysis is ongoing to evaluate changes in systemic immune response. These results support the synergistic effect of the combination in the orthotopic model.

Conclusions: Combining DaRT with PD-1 blockade significantly improves tumor response, resulting in a substantial tumor regression rate. Analysis of serum cytokine levels will provide further insight into the immunomodulatory effects of this combination. This provides a strong rationale for clinical trials evaluating this combination in HNSCC.