Abstract B140: Positron emission tomography-guided photodynamic therapy with biodegradable silica nanoparticles for personalized cancer immunotherapy

Abstract

Recent clinical trials with neoantigen-based vaccines have shown the feasibility and potential of personalized cancer immunotherapy. Photodynamic therapy (PDT), which utilizes photosensitizer and laser irradiation to produce reactive oxygen species, has been widely explored for local cancer treatment. In addition, positron emission tomography (PET) is a highly sensitive and noninvasive imaging method that can visualize solid tumors while allowing for quantitative analysis of drug biodistribution. In this work, we aimed to combine vaccination and PET imaging-guided PDT as an effective combination platform for personalized cancer immunotherapy. We have synthesized biodegradable silica nanoparticles (bMSN) loaded with neoantigen, CpG oligodeoxynucleotide (a potent Toll-like recetor-9 agonist) and chlorin e6 (a widely used photosensitizer). Using PET imaging, we have shown that bMSN effectively accumulates in MC-38 colon carcinoma tumors after intravenous administration in vivo. Subsequent PDT with 660 nm laser irradiation eliminated tumors, resulting in the release of tumor antigens and danger signals that promoted recruitment of dendritic cells to PDT-treated sites. The bMSN nanoplatform sustain-released neoantigen and CpG oligodeoxynucleotide, while activating DCs and enhancing neoantigen-specific cytotoxic CD8+ T-cell responses and their infiltration into tumors. In mice bearing two contralateral MC-38 tumors, the combination of vaccination and PDT completely eradicated locally treated, large MC-38 tumors while significantly delaying the growth of distant, untreated tumors. Our findings suggest that bMSN is a promising immunotherapeutic platform for combining imaging, vaccination, and PDT for treatment of advanced cancer. Citation Format: Cheng Xu, James Moon. Positron emission tomography-guided photodynamic therapy with biodegradable silica nanoparticles for personalized cancer immunotherapy [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B140.