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논문 기본 정보

자료유형
학술저널
저자정보
Jiajia Zhang (Tongji University School of Medicine People’s Republic of China.) Feize Li (Sichuan University) Yuzhen Yin (Tongji University School of Medicine People’s Republic of China.) Ning Liu (Sichuan University) Mengqin Zhu (Tongji University School of Medicine People’s Republic of China.) Han Zhang (Tongji University School of Medicine People’s Republic of China.) Weihao Liu (Sichuan University Chengdu 610064 People’s Republic of China.) Mengdie Yang (Tongji University School of Medicine People’s Republic of China.) Shanshan Qin (Tongji University School of Medicine People’s Republic of China.) Xin Fan (Tongji University School of Medicine People’s Republic of China.) Yuanyou Yang (Sichuan University) Kun Zhang (Tongji University) Fei Yu (Tongji University School of Medicine People’s Republic of China.)
저널정보
한국생체재료학회 생체재료학회지 생체재료학회지 제26권 제4호
발행연도
2022.12
수록면
870 - 884 (15page)
DOI
https://doi.org/10.1186/s40824-022-00290-6

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Background: Astatine-211 is an α-emitter with high-energy α-ray and high cytotoxicity for cancer cells. However, the targeted alpha therapy (TAT) also suffers from insufficient systematic immune activation, resulting in tumor metastasis and relapse. Combined immune checkpoint blockade (ICB) with chemodynamic therapy (CDT) could boost antitu mor immunity, which may magnify the immune responses of TAT. This study aims to discourage tumor metastasis and relapse by tri-model TAT-CDT-ICB strategy. Methods: We successfully designed Mn-based radioimmunotherapy promoters (211At-ATE-MnO2-BSA), which are consisting of 211At, MnO2 and bovine serum albumin (BSA). The efficacy of 211At-ATE-MnO2-BSA was studied as mono therapy or in combination with anti-PD-L1 in both metastatic and relapse models. The immune effects of radioimmu notherapy promoters on cytotoxic T lymphocytes and dendritic cells (DCs) were analyzed by flow cytometry. Enzyme linked immunosorbent assay and immunofluorescence were used to explore the underlying mechanism. Results: Such radioimmunotherapy promoters could not only enhance the therapeutic outcomes of TAT and CDT, but also induce robust anti-cancer immune activity by activating dendritic cells. More intriguingly, 211At-ATE-MnO2-BSA could effectively suppress the growths of primary tumors and distant tumors when combined with immune checkpoint inhibitors. Conclusions: The tri-model TAT-CDT-ICB strategy provides a long-term immunological memory, which can protect against tumor rechallenge after eliminating original tumors. Therefore, this work presents a novel approach for TAT CDT-ICB tri-modal cancer therapy with repressed metastasis and relapse in clinics.

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