Work

596 A preclinical murine model investigation of the synergistic effect of mechanical focused ultrasound ablation and immune check point inhibitor anti-PD1 for osteosarcoma

Year: 2026

Type: conference-abstract

Abstract: Background Osteosarcoma (OS) is the most common malignant bone tumor in pediatric cancer patients, with a 70% 5-year survival rate which has not improved in decades due to resistant pulmonary metastatic disease. The proposed project addresses the unmet clinical need for improving treatment optionsdeveloping the combination treatment of mechanical focused ultrasound ablation (mFUS) with the immune check point inhibitor anti-PD1. Our team has previously demonstrated the success of ablating OS with mFUS in canine patients with spontaneously occurring OS and establishing local tumor control. We hypothesize that the synergistic effect of mFUS + anti-PD1 immunotherapy will result in robust local tumor control and mitigation of metastatic disease.Methods The C3H/HeN- DLM8 syngeneic orthotopic OS murine model was employed to test three mFUS doses (low, medium, and high) in combination with anti-PD1 to identify the treatment paradigm which results in superior tumor control.Results Our results indicate that low and medium dose combination therapies are superior to mFUS and anti-PD1 monotherapies and no treatment. We observed greater overall tumor progression and body weight loss in mFUS only mice compared to combination treatment mice, especially in the high dose group. The medium combination group (n = 8) had an average 10% body weight gain post treatment. Additionally, this group had statistically significantly less tumor progression compared to medium and high mFUS only, with n = 6/8 of mice demonstrating tumor regression, and of those mice n = 4/6 demonstrated complete regression. The largest tumor diameter was statistically significantly decreased in the medium combination group compared to all experimental and control groups. The high mFUS dose resulted in tumor progression with and without anti-PD1.Conclusions Clinically, solid tumors classified as immunologically cold are often refractory to immune checkpoint inhibitors, but our results suggest a positive synergistic effect of the mFUS + anti-PD1 therapy in a dose dependent manner. This preclinical study warrants future investigations aimed at evaluation of local and systemic immunomodulation, and use of the combination treatment strategy with canine patients with spontaneously occurring OS which serve as a valuable comparative oncology model for human OS.Ethics Approval All experiments in this study were conducted under approval from the Virginia Tech Institutional Animal Care and Use Committee (protocol number 25-162).

Source: Journal for ImmunoTherapy of Cancer

DOI: 10.1136/jitc-2026-sitc2026.0596