Abstract 5081: Immune sensitization of melanoma to checkpoint inhibitor therapy using acoustically active nanoparticles

Abstract

Abstract Advanced melanoma remains the most fatal form of skin cancer with novel therapeutic approaches required to treat inoperable metastatic lesions. While immunotherapies have shown promise in improving long-term melanoma survival, its treatment efficacy is limited, with only 50% of patients responding. Focused ultrasound (FUS) offers as a non-invasive strategy for targeted tumor ablation, thereby strengthening immunotherapy efficacy by release of tumor associated materials. However, control over tumor material release through FUS, without causing excessive thermal damage to surrounding healthy tissue remains challenging. To address this challenge, our group has previously developed acoustically active nanoparticles (AANPs) responsive to low intensity ultrasound for mechanical tumor ablation by generating strong and durable acoustic cavitation in the tumor tissue. Building upon previous success with AANPs, our current work focuses on sensitizing melanoma tumors to checkpoint inhibitor therapy by releasing tumor antigens into circulation using AANPs and FUS. Our findings revealed sensitization of an immunologically cold B16-F10 metastatic melanoma tumors following treatment, which resulted in a notable 12-day stall in tumor growth. When combined with immune checkpoint inhibitors α-PD-L1 and α-CTLA-4, this approach showed a complete response in B16-F10 bearing mice with impressive memory immune response upon a tumor rechallenge. Herein, these novel AANPs represent a promising advancement to enable accurate immune surveillance by boosting the release of tumor antigens and offers new strategies for improved immunotherapy of melanoma and other solid tumors. Citation Format: Michael Ian Henderson, Li Xiang, Samuel Drennan, Xin Yi, Jared Fischer, Adem Yildirim. Immune sensitization of melanoma to checkpoint inhibitor therapy using acoustically active nanoparticles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5081.