Defining the mechanism of toxicity from loss of immune checkpoints

通过免疫检查点阻断，癌症治疗得到了改善，增强了免疫系统靶向肿瘤的能力。使用修饰的mRNA疫苗的新疗法有望获得更好的结果。然而，这些治疗有时会通过激活免疫细胞而引起严重的副作用，这些免疫细胞会错误地攻击身体自身的组织。我们的研究旨在了解这些副作用发生的原因，并找到使这些疗法更安全的方法。我们的方法：1.研究患者：o我们检查了接受免疫检查点阻断或修饰的mRNA疫苗治疗的患者，以了解他们的免疫系统如何受到影响。o通过将他们与患有影响免疫系统的罕见遗传疾病的人进行比较，我们证实了副作用是由治疗直接引起的。使用动物模型：o我们使用小鼠来模拟免疫系统问题，帮助我们研究其原因。o这些模型使我们能够测试不同的治疗和免疫调节，以预防或减少副作用。我们的目标：将患者研究与动物研究相结合，我们的目标是提高癌症治疗的安全性。了解这些副作用将有助于我们开发出既有效又安全的疗法，从而为癌症患者带来更好的结果。

Cancer treatment has improved with immune checkpoint blockade, boosting the immune system’s ability to target tumours. New therapies using modified mRNA vaccines promise even better outcomes. However, these treatments can sometimes cause serious side effects by activating immune cells that mistakenly attack the body’s own tissues. Our research aims to understand why these side effects happen and find ways to make these therapies safer.Our Approach:1. Studying Patients:o We examine patients treated with immune checkpoint blockade or modified mRNA vaccines to see how their immune systems are affected.o By comparing them to people with rare genetic diseases affecting the immune system, we confirm that the side effects are directly caused by the treatments.2. Using Animal Models:o We use mice to model immune system problems, helping us study their causes.o These models allow us to test different treatments and immune adjustments to prevent or reduce side effects.Our Goal:Combining patient studies with animal research, we aim to improve the safety of cancer treatments. Understanding these side effects will help us develop therapies that are both effective and safe, leading to better outcomes for cancer patients.