机器人 1 特异性 CAR-NK 免疫疗法增强了 I 种子近距离放疗在人胰腺癌细胞原位模型中的疗效。

Robo1-specific CAR-NK Immunotherapy Enhances Efficacy of I Seed Brachytherapy in an Orthotopic Mouse Model of Human Pancreatic Carcinoma.

机构信息

Department of Radiology, School of Radiation Medicine and Protection, Medical College of Soochow University, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou, P.R. China.

Department of Radiobiology, Ruijin Hospital Luwan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.

出版信息

Anticancer Res. 2019 Nov;39(11):5919-5925. doi: 10.21873/anticanres.13796.

DOI:10.21873/anticanres.13796

PMID:31704816

Abstract

BACKGROUND/AIM: The aim of the current study was to investigate the synergistic efficacy of Robo1 bichimeric antigen receptor-natural killer cell (BiCAR-NK) immunotherapy and I seed brachytherapy in an orthotopic pancreatic cancer mouse model.

MATERIALS AND METHODS

The orthotopic pancreatic tumor model was established with human pancreatic cancer BxPC-3 cells expressing red fluorescent protein. The mice were treated with I seed implantation alone or the combination of I seeds with Robo1-specific CAR-NK cells. To assess tumor inhibition, in vivo fluorescence imaging was conducted. 7 Tesla magnetic resonance (7T-MR) scanning was applied to measure the changes in the metabolic profiles of tumor tissues.

RESULTS

Tumor size was significantly reduced in the I and I +CAR-NK treated group compared to the untreated group (p<0.05). The I seed +CAR-NK treated group showed significantly higher tumor reduction than I seed treatment alone (p<0.05). T1 diffusion weighted imaging (T1DWI) sequence showed that the tumors of the I +BiCAR-NK treated group had a significantly higher grey scale value than the tumors from the untreated control and the group treated with I seed alone (p<0.05).

CONCLUSION

Robo1 specific CAR-NK immunotherapy enhances efficacy of I seed brachytherapy in an orthotopic pancreatic cancer mouse model.

摘要

背景/目的：本研究旨在探讨 Robo1 双特异性抗原受体自然杀伤细胞（BiCAR-NK）免疫疗法与 I 种子近距离放疗在原位胰腺癌小鼠模型中的协同疗效。

材料与方法

用表达红色荧光蛋白的人胰腺癌细胞 BxPC-3 建立原位胰腺肿瘤模型。将小鼠单独用 I 种子植入或用 Robo1 特异性 CAR-NK 细胞联合 I 种子进行治疗。为了评估肿瘤抑制作用，进行了体内荧光成像。应用 7 特斯拉磁共振（7T-MR）扫描测量肿瘤组织代谢谱的变化。

结果

与未治疗组相比，I 种子和 I +CAR-NK 治疗组的肿瘤体积明显减小（p<0.05）。I 种子+CAR-NK 治疗组的肿瘤缩小程度明显高于 I 种子单独治疗组（p<0.05）。T1 扩散加权成像（T1DWI）序列显示，与未治疗对照组和仅用 I 种子治疗组相比，I +BiCAR-NK 治疗组的肿瘤灰度值明显更高（p<0.05）。