Adeno-associated Virus-mediated Local Delivery of LIGHT Suppresses Tumorigenesis in a Murine Cervical Cancer Model

作者:Maitituoheti, Mayinuer; Li, Yan; Wang, Wenwen; Wang, Wei; Han, Lingfei; Yang, Runfeng; Wang, Tian; Wu, Zhangying; Ma, Ding; Wang, Shixuan*
来源:Journal of Immunotherapy, 2011, 34(8): 581-587.
DOI:10.1097/CJI.0b013e31822b9fe0

摘要

LIGHT is a tumor necrosis factor superfamily ligand that is considered as a promising candidate for cancer therapy. It has a potent antitumor activity through establishing lymphoid-like tissues inside tumor sites and recruiting naive T cells into the tumor. In this study, we examined the possibility of antitumor activity by expressing LIGHT in cervical cancer (CC) model. A recombinant adeno-associated virus (AAV) vector was chosen for the transfer, based on its transfection efficiency and lack of detectable pathology. In vitro transfer of recombinant AAV vector expressing LIGHT (AAV-LIGHT) stimulated T-lymphocyte proliferation and activation. AAV-mediated gene transfer of LIGHT by intratumoral injection exerted a very potent antitumor effect against preexisting TC-1 cell CC in C57BL/6 mice. This study confirmed that AAV-LIGHT regressed tumor growth by activating cytotoxic T lymphocyte, enhancing infiltration of inflammatory cells in tumor and increasing stimulatory cytokine expression in tumor microenvironment. Therefore, AAV-LIGHT therapy might have potential utility for the treatment of CC.