Zr 标记抗 CD8 cys-二抗体正电子发射断层扫描成像显示溶瘤病毒治疗胶质母细胞瘤小鼠模型中 CD8 细胞浸润。
Positron emission tomography imaging with Zr-labeled anti-CD8 cys-diabody reveals CD8 cell infiltration during oncolytic virus therapy in a glioma murine model.
机构信息
Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Radiology, University of Alabama at Birmingham, Volker Hall G082, 1670 University Boulevard, Birmingham, AL, 35294, USA.
出版信息
Sci Rep. 2021 Jul 28;11(1):15384. doi: 10.1038/s41598-021-94887-x.
Determination of treatment response to immunotherapy in glioblastoma multiforme (GBM) is a process which can take months. Detection of CD8 T cell recruitment to the tumor with a noninvasive imaging modality such as positron emission tomography (PET) may allow for tumor characterization and early evaluation of therapeutic response to immunotherapy. In this study, we utilized Zr-labeled anti-CD8 cys-diabody-PET to provide proof-of-concept to detect CD8 T cell immune response to oncolytic herpes simplex virus (oHSV) M002 immunotherapy in a syngeneic GBM model. Immunocompetent mice (n = 16) were implanted intracranially with GSC005 GBM tumors, and treated with intratumoral injection of oHSV M002 or saline control. An additional non-tumor bearing cohort (n = 4) receiving oHSV M002 treatment was also evaluated. Mice were injected with Zr-labeled anti-CD8 cys-diabody seven days post oHSV administration and imaged with a preclinical PET scanner. Standardized uptake value (SUV) was quantified. Ex vivo tissue analyses included autoradiography and immunohistochemistry. PET imaging showed significantly higher SUV in tumors which had been treated with M002 compared to those without M002 treatment (p = 0.0207) and the non-tumor bearing M002 treated group (p = 0.0021). Accumulation in target areas, especially the spleen, was significantly reduced by blocking with the non-labeled diabody (p < 0.001). Radioactive probe accumulation in brains was consistent with CD8 cell trafficking patterns after oHSV treatment. This PET imaging strategy could aid in distinguishing responders from non-responders during immunotherapy of GBM.
胶质母细胞瘤(GBM)的免疫治疗反应的确定是一个需要数月时间的过程。利用正电子发射断层扫描(PET)等非侵入性成像方式检测 CD8 T 细胞向肿瘤的募集情况,可能有助于肿瘤特征分析和对免疫治疗的早期疗效评估。在这项研究中,我们利用 Zr 标记的抗 CD8 cys-二抗-PET 来提供概念验证,以检测溶瘤单纯疱疹病毒(oHSV)M002 免疫疗法在同种异体 GBM 模型中对 CD8 T 细胞免疫反应的作用。免疫功能正常的小鼠(n=16)颅内植入 GSC005 GBM 肿瘤,并接受肿瘤内注射 oHSV M002 或生理盐水对照治疗。还评估了另外一组未携带肿瘤的接受 oHSV M002 治疗的小鼠(n=4)。在 oHSV 给药后 7 天,用 Zr 标记的抗 CD8 cys-二抗注射小鼠,并使用临床前 PET 扫描仪进行成像。量化标准摄取值(SUV)。离体组织分析包括放射自显影和免疫组织化学。PET 成像显示,与未接受 M002 治疗的肿瘤相比,接受 M002 治疗的肿瘤 SUV 值显著更高(p=0.0207),且非肿瘤携带的 M002 治疗组 SUV 值也更高(p=0.0021)。用未标记的二抗阻断后,目标区域(尤其是脾脏)的放射性探针积累显著减少(p<0.001)。oHSV 治疗后大脑中放射性探针的积累与 CD8 细胞的迁移模式一致。这种 PET 成像策略可能有助于在 GBM 的免疫治疗中区分反应者和非反应者。
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