Anti-tumor immunity enhancement by photodynamic therapy with talaporfin sodium and anti-programmed death 1 antibody.

IF 5.3 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Makiko Sasaki, Mamoru Tanaka, Yuki Kojima, Hirotada Nishie, Takaya Shimura, Eiji Kubota, Hiromi Kataoka
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引用次数: 6

Abstract

Photodynamic therapy (PDT) is a relatively non-invasive anti-cancer therapy that employs a photosensitizer with a specific wavelength of light irradiation. PDT induces direct cell killing and enhancement effects on tumor immunity, but its underlying mechanism remains unknown. Here, we perform a basic analysis of the anti-tumor effect of talaporfin sodium (TS)-PDT as well as its synergism with the immune checkpoint inhibitor anti-programmed death 1 (anti-PD-1) antibody. We estimate the cell death mechanism induced by TS-PDT and the induction of damage-associated molecular patterns (DAMPs) by TS-PDT in vitro. We establish a syngeneic mouse model of bilateral flank tumors and verify the enhancement of the abscopal effect on the non-irradiated side. TS-PDT induced apoptosis, necrosis, and autophagy-associated cell death in vitro. TS-PDT induced the release and/or expression of DAMPs in vitro. Tumor growth was inhibited in the TS-PDT and anti-PD-1 antibody combination group compared with other single-treatment or non-treatment groups in vivo. In summary, TS-PDT induces the release and/or expression of DAMPs, indicating that it activates innate immunity. PD-1 blockage enhances the anti-tumor immunity induced by TS-PDT. Thus, our results demonstrate that the combination of TS-PDT and anti-PD-1 antibody can potentially be used for anti-tumor therapy.

Abstract Image

Abstract Image

Abstract Image

他拉波芬钠光动力治疗与抗程序性死亡1抗体增强抗肿瘤免疫。
光动力疗法(PDT)是一种相对非侵入性的抗癌疗法,它使用具有特定波长光照射的光敏剂。PDT诱导细胞直接杀伤和增强肿瘤免疫,但其潜在机制尚不清楚。在这里,我们对塔拉波芬钠(TS)-PDT的抗肿瘤作用及其与免疫检查点抑制剂抗程序性死亡1 (anti-PD-1)抗体的协同作用进行了基本分析。我们在体外估计了TS-PDT诱导的细胞死亡机制以及TS-PDT诱导的损伤相关分子模式(DAMPs)。我们建立了小鼠双侧侧腹肿瘤的同基因模型,并验证了对未照射侧的体外效应的增强。TS-PDT在体外诱导细胞凋亡、坏死和自噬相关细胞死亡。TS-PDT诱导体外DAMPs的释放和/或表达。TS-PDT联合抗pd -1抗体组与其他单药组或非治疗组相比,体内肿瘤生长受到抑制。综上所述,TS-PDT诱导DAMPs的释放和/或表达,表明它激活了先天免疫。阻断PD-1可增强TS-PDT诱导的抗肿瘤免疫。因此,我们的研究结果表明,TS-PDT与抗pd -1抗体的结合可能用于抗肿瘤治疗。
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来源期刊
Molecular Therapy Oncolytics
Molecular Therapy Oncolytics Medicine-Oncology
CiteScore
10.90
自引率
3.50%
发文量
152
审稿时长
6 weeks
期刊介绍: Molecular Therapy — Oncolytics is an international, online-only, open access journal focusing on the development and clinical testing of viral, cellular, and other biological therapies targeting cancer.
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