Single Treatment Boiling Histotripsy Focused Ultrasound Ablation Neither Negates nor Enhances the Activity of α-CD40 in a Pancreatic Cancer Model

OBJECTIVE: Pancreatic adenocarcinoma (PDAC) tumors are often unresectable and do not respond to standard anti-cancer treatments. Boiling histotripsy (BH) is a mechanical focused ultrasound ablation regimen that can target non-operable tumors. BH is a non-invasive procedure that might synergize with immunotherapies being developed for PDAC. We reasoned that BH-mediated release of tumor antigen and damage-associated molecular patterns would augment tumor immunity and cooperate with α-CD40 therapy. METHODS: We explored the efficacy of BH ablation either as monotherapy for PDAC or in combination with systemically administered α-CD40 agonistic antibodies in controlling tumor outgrowth. We further assessed the changes in the tumor immune compartment and the ability of BH to release tumor antigens by flow cytometry. RESULTS: T cells to the tumor microenvironment, suggesting that antibody access to the ablated tissue was not obstructed. CONCLUSION: Our findings indicate that PDAC tumor progression cannot be halted by BH ablation using sub-total ablation, and that the BH treatment regimen utilized in this study has limited immunogenicity. SIGNIFICANCE: Our discoveries attest to the need for optimizing BH ablation protocols to unlock its anti-tumor potential.