过继性细胞移植
正电子发射断层摄影术
癌症研究
离体
免疫疗法
归巢(生物学)
抗原
体内分布
分子成像
细胞毒性T细胞
嵌合抗原受体
T细胞
体内
生物
病理
体外
免疫学
医学
免疫系统
核医学
生物技术
生物化学
生态学
作者
Yu Liu,Xiaoying Lv,Xingfu Song,Fuqiang Shao,Hao Ji,Yirui Zhang,Pengxin Qiao,Qingyao Liu,Xiaotian Xia,Ping Lei,Yongkang Gai,Xiaoli Lan
标识
DOI:10.1007/s00259-022-05886-7
摘要
γδ T cell-based immunotherapy has been rolled out as a promising treatment strategy for malignant tumors due to their potent anti-tumor cytotoxicity, ease of expansion, and unrestricted MHC feature. However, the dynamics and outcomes of γδ T cells in tumor sites are poorly understood. Reported strategies rely on ex vivo biolabeling, significantly limiting the application of γδ T cell molecular imaging. Herein, we investigated whether VLA-4 (very late antigen-4), a crucial component in the effective trafficking of lymphocytes, could serve as a biomarker to non-invasively visualize γδ T cells.VLA-4-targeted tracer, 68 Ga-LLP2A, was evaluated in MDA-MB-231- and A549-bearing mice with adoptive transfer of γδ T cells by longitudinal PET/CT imaging. Imaging data were verified by ex vivo biodistribution studies, and the co-localization of CD3 and VLA-4 was validated by immunohistochemistry studies.68 Ga-LLP2A showed high specificity to VLA-4-expressing γδ T cells in both in vitro and tumor-bearing mice with adoptive transfer of γδ T cells. Longitudinal PET imaging of 68 Ga-LLP2A in tumor-bearing mice with adoptive transfer of γδ T cells showed an increasing tumor tracer uptake, revealing the tumor-specific homing of γδ T cells. The presence of VLA-4-expressing γδ T cells in tumors was confirmed via histological analysis.To the best of our knowledge, we reported the first molecular probe, 68 Ga-LLP2A, for in vivo imaging of γδ T cells in live tumors, which advances PET imaging of γδ T cells and supports the translation of imaging agents for immunotherapeutic monitoring.
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