Purging metastases in lymphoid organs using a combination of antigen-nonspecific adoptive T cell therapy, oncolytic virotherapy and immunotherapy
Purging metastases in lymphoid organs using a combination of antigen-nonspecific adoptive T cell therapy, oncolytic virotherapy and immunotherapy
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DOI：
10.1038/nm1681
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发表时间：
2008-01-01
期刊：
影响因子：
82.9
通讯作者：
Vile, Richard G.
中科院分区：
文献类型：
--
作者：
Qiao, Jian;Kottke, Timothy;Vile, Richard G.
在许多常见的癌症中，继发性肿瘤通过淋巴结的传播对受影响的个体构成最重大的威胁。转移细胞通常通过模仿造血细胞运输到外周淋巴器官的分子机制到达淋巴结。因此，我们利用幼稚T细胞运输，以便将溶瘤病毒陪伴到携带转移细胞的淋巴器官。转移负荷最初通过病毒溶瘤降低，然后被根除，因为淋巴结和脾脏中的肿瘤细胞杀伤产生保护性抗肿瘤免疫。淋巴结清除肿瘤细胞是可能的，即使在病毒免疫小鼠。将载有溶瘤病毒的正常T细胞连续转移到患有癌症的个体中在技术上容易实现，以减少转移的分布并原位接种受影响的个体以对抗微转移疾病。因此，这种过继性转移在辅助治疗环境中对许多不同的癌症类型具有很大的治疗影响。
In many common cancers, dissemination of secondary tumors via the lymph nodes poses the most significant threat to the affected individual. Metastatic cells often reach the lymph nodes by mimicking the molecular mechanisms used by hematopoietic cells to traffic to peripheral lymphoid organs. Therefore, we exploited naive T cell trafficking in order to chaperone an oncolytic virus to lymphoid organs harboring metastatic cells. Metastatic burden was initially reduced by viral oncolysis and was then eradicated, as tumor cell killing in the lymph node and spleen generated protective antitumor immunity. Lymph node purging of tumor cells was possible even in virus-immune mice. Adoptive transfer of normal T cells loaded with oncolytic virus into individuals with cancer would be technically easy to implement both to reduce the distribution of metastases and to vaccinate the affected individual in situ against micrometastatic disease. As such, this adoptive transfer could have a great therapeutic impact, in the adjuvant setting, on many different cancer types.