Qiao Jian, Kottke Timothy, Willmon Candice, Galivo Feorillo, Wongthida Phonphimon, Diaz Rosa Maria, Thompson Jill, Ryno Pamela, Barber Glen N, Chester John, Selby Peter, Harrington Kevin, Melcher Alan, Vile Richard G
Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55905, USA.
Nat Med. 2008 Jan;14(1):37-44. doi: 10.1038/nm1681. Epub 2007 Dec 9.
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.
在许多常见癌症中,通过淋巴结扩散继发性肿瘤对患者构成了最严重的威胁。转移细胞常常通过模仿造血细胞进入外周淋巴器官的分子机制到达淋巴结。因此,我们利用天然T细胞的迁移,将一种溶瘤病毒运送至含有转移细胞的淋巴器官。转移性肿瘤负荷最初因病毒溶瘤作用而降低,随后被根除,因为淋巴结和脾脏中的肿瘤细胞杀伤产生了保护性抗肿瘤免疫。即使在对病毒免疫的小鼠中,也能够清除淋巴结中的肿瘤细胞。将负载溶瘤病毒的正常T细胞过继转移至癌症患者体内,在技术上易于实施,既能减少转移灶的扩散,又能在原位使患者针对微转移疾病产生免疫。因此,这种过继转移在辅助治疗中可能对许多不同类型的癌症产生巨大的治疗效果。