Next Generation Glioma Treatments using Direct Light Therapy (GlioLighT)

神经胶质瘤是一种极其致命的癌症，主要是由于大脑的不可接近性和肿瘤部位细胞的扩散。这些弥漫性细胞通常在大脑中嵌入太深，无法通过当前手段安全地移除。靶向活性氧（ROS）产生是一种有前途的胶质瘤治疗形式，可选择性消除胶质瘤，包括弥漫性细胞。然而，靶向ROS产生的唯一当前手段是光动力疗法（PDT），其使用昂贵且潜在有毒的光敏剂（PS）产生ROS，所述光敏剂对远距离扩散的细胞无效并引入许多治疗限制。GlioLighT提出了一种新的靶向ROS产生的替代形式：直接光疗法（DLT）。DLT使用1267 nm光在神经胶质瘤细胞中产生1 O2物质，而不依赖于PS。去除PS将彻底改变胶质瘤治疗，使新的治疗方式能够大大提高疗效，早期干预选择，所有这些都降低了成本和复杂性。然而，尽管DLT的原理已经得到证实，但人们对DLT如何实现其抗癌作用或其治疗益处的程度知之甚少。利用数十年积累的PDT知识和技术发展，GlioLighT将独立研究DLT技术并与PDT进行比较。将研究DLT对神经胶质瘤和脑的影响，重点是免疫原性，以确定DLT的疗效、安全性和作用机制。将开发新型超短脉冲（USP）光源，以最大限度地提高光学穿透力并最大限度地降低安全风险，确保DLT适合临床采用。最后，临床前GlioLighT输送和传感系统（pcGlio-DSS）的开发为下一步的临床转化做好了准备，这将使DLT更接近于大幅改善欧洲和全球神经胶质瘤治疗的飞跃。

Glioma is an extremely lethal cancer, due largely to the inaccessible nature of the brain and diffusion of cells from the tumour site. These diffuse cells are usually too deeply embedded in the brain to safely remove by current means. Targeted Reactive Oxygen Species (ROS) generation is a promising form of glioma treatment to selectively eliminate glioma, including diffuse cells. However, the only current means of targeted ROS generation is photodynamic therapy (PDT) which generates ROS using expensive and potentially toxic photosensitisers (PS) which are ineffective against distant diffused cells and introduce many treatment limitations. GlioLighT proposes a novel alternative form of targeted ROS generation: Direct Light Therapy (DLT). DLT uses 1267nm light to generate 1O2 species in glioma cells without dependency on a PS. The removal of PS will revolutionise glioma treatment, enabling novel treatment modalities to vastly improve efficacy, earlier intervention options, all at reduced cost and complexity. However, whilst the principles of DLT have been demonstrated, little is known about how DLT achieves its anti-cancer effects, or the extent of its therapeutic benefits. Leveraging decades of accumulated PDT knowledge and technology development, GlioLighT will study DLT technology both independently and compared to PDT. The effect of DLT on glioma and the brain, focusing on immunogenicity, will be studied to determine DLT’s efficacy, safety, and mechanisms of action. Novel ultrashort pulse (USP) light sources will be developed to maximise optical penetration and minimise safety risk, ensuring DLT is suited for clinical adoption. Lastly, the development of the preclinical GlioLighT delivery and sensing system (pcGlio-DSS) ready for the next steps of clinical translation, will bring DLT a leap closer to vastly improving glioma treatment in Europe and worldwide.