Department of Clinical Pathology, Singapore General Hospital, Singapore.
Department of Hematology, Singapore General Hospital, Singapore.
Immunotherapy. 2018 Feb 1;10(4):255-263. doi: 10.2217/imt-2017-0080.
The new radioimmunotherapeutic regime GAP15R aims to stimulate glucocorticoid-induced TNF-related protein (G) to overcome Treg suppression; add IFN-α (A) to promote inflammatory milieu; block PD1 (P) to disinhibit T effector cytotoxicity; add IL-15 (15) to enhance danger signals & T-cell expansion; and apply radiation (R) at critical time point to sustain localized inflammation. Patients & methods/materials & methods: This was tested in a murine 4T1 metastatic breast carcinoma model given GAP15R with regular monitoring of tumor volume and complications.
We had demonstrated long-term complete remission up to 50% of treated mice, which is not associated with major treatment-related complication, in cases with specific tumor burden.
GAP15R is efficacious with potential to be applicable to other tumors.
新型放射免疫治疗方案 GAP15R 旨在刺激糖皮质激素诱导的肿瘤坏死因子相关蛋白(G)以克服 Treg 抑制;添加 IFN-α(A)以促进炎症微环境;阻断 PD1(P)以解除 T 效应细胞细胞毒性抑制;添加 IL-15(15)以增强危险信号和 T 细胞扩增;并在关键时间点应用辐射(R)以维持局部炎症。
患者和方法/材料和方法:这在给予 GAP15R 的 4T1 转移性乳腺癌小鼠模型中进行了测试,并定期监测肿瘤体积和并发症。
我们已经证明,在特定肿瘤负荷的情况下,高达 50%的治疗小鼠出现长期完全缓解,且与主要治疗相关并发症无关。
GAP15R 有效,有潜力应用于其他肿瘤。