Abstract B78: NIR light-triggered photoimmunotherapy selectively destroy tumor cells in a clinically relevant desmoplastic heterocellular model

Abstract

Abstract Near-infrared light-triggered photoimmunotherapy, utilizing the simultaneous presence of light and targeted conjugates, has emerged as a promising approach to impart selective cytotoxicity, especially for more complex nanoconstructs. Targeted immunoconjugates promise unique capabilities of combining multiple therapeutic agents within a single nanoplatform and promise great advances in revolutionizing cancer treatments, promoting selective drug localization and photo-triggered release of secondary agents to tumors cells that overexpress specific receptors. This study has utilized smart, liposome-based photoactivatable multiagent nanoconjugates, doped with a photoactivatable chromophore benzoporphyrin derivative (BPD) labeled with an active targeting ligand cetuximab to target the EGFR receptor (overexpressed on various cancer cells) for quantitative molecular imaging to measure the true in vivo receptor specificity and localized photodynamic therapy following NIR activation, that further can trigger the release of encapsulated payload to pancreatic cancer spheroids. In an in vivo model, these targeted nanoconstructs demonstrate substantial pancreatic tumor necrosis in a receptor-specific manner and modulate the collagen content in desmoplastic model of pancreatic ductal adenocarcinoma (MIA PaCa-2) in the presence of patient-derived pancreatic cancer-associated fibroblasts (PCAFs). This study establishes a tunable path towards optimally effective multiagent nanoconjugates for tumor-specific accumulation and targeted destruction of cancer cells in complex cancer model to enhance the therapeutic index of the administrated drugs. Citation Format: Shazia Bano. NIR light-triggered photoimmunotherapy selectively destroy tumor cells in a clinically relevant desmoplastic heterocellular model [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr B78.