ET-9 Development of photosensitive antibodies for near-infrared light immunotherapy targeting EGFR and IL13Rα2 of malignant gliomas and investigation of their photodynamic cytotoxic activity in vitro. (6th December 2021)

• Record Type: Journal Article
• Authors: Nonoguchi, Naosuke; Kambara, Akihiro; Kimura, Seigo; Kawabata, Shinji; Yagi, Ryokichi; Ikeda, Naokado; Furuse, Motomasa; Wanibuchi, Masahiko
• Is Part Of: Neuro-oncology advances. Volume 3(2021)Supplement 6
• Page Start: vi5
• Page End: vi5
• Publication Date: 2021-12-06
• Subjects: Photoimmunotherapy -- EGFR -- IL13Rα2; 616.99481
• DOI: 10.1093/noajnl/vdab159.019
• Languages: English
• ISSNs: 2632-2498

Abstract

Abstract: Introduction: Near-Infrared Photoimmunotherapy (NIR-PIT) is a recently developed hybrid cancer therapy based on photodynamic cytotoxicity and anti-tumor immunopotentiation, utilizing a photosensitive antibody drug (PSAD). A global Phase III trial of NIR-PIT with an anti-EGFR-PSAD in patients with recurrent head and neck squamous cell carcinoma (HNSCC) is already underway, and NIR-PIT is expected to have therapeutic applications also in malignant gliomas. Methods: In this study, monoclonal antibodies to EGFR and IL13Rα2 were conjugated to the photosensitive dye IRDye700DX (IR700) to produce PSADs (EGFR-Ab/IR700 and IL13Rα2-Ab/IR700) and in vitro PDT assays using these PSADs were performed on four human glioma cell lines (U87MG, U251, U138, A172).Five groups were studied: EGFR-Ab/IR700 monotherapy: 5 μg/ml or 10 μg/ml, IL13Rα2-Ab/IR700 monotherapy: 5 μg/ml or 10 μg/ml, and EGFR-Ab/IR700: 5 μg/ml + IL13Rα2-Ab/IR700: 5 μg/ml combination therapy. The cytotoxic activity of each group was compared after irradiation with 690 nm light at 16 J/cm2. Results: Significantly higher cytotoxic activity was observed in all four glioma cell lines when EGFR-Ab/IR700 and IL13Rα2-Ab/IR700 were used in combination at 5 μg/ml each, than when each PSAD was treated with a doubled dose (10 μg/ml).Conclusion: Malignant gliomas show extensive cellular heterogeneity with diverse expression of cell surface antigens. The present results suggest that a therapeutic strategy using several different photosensitive antibodies simultaneously may lead to the release of tumor antigens from a greater number of tumor cells, resulting in a more efficient host immune response for therapeutic purposes.