Immunotherapy: Open Access
Open Access
ISSN: 2471-9552
ISSN: 2471-9552
Shenzhen International Institute for Biomedical Research, 140 Jinye Ave. Building A10, Dapeng New District, Shenzhen, Guangdong 518116, China
Research
Enhancement of Oncolytic Activity of oHSV Expressing IL-12 and Anti PD-1 Antibody by Concurrent Administration of Exosomes Carrying CTLA-4
miRNA
Author(s): Runbin Yan, Xusha Zhou, Xiaoqing Chen, Xianjie Liu, Yuxin Tang, Jie Ma, Lei Wang, Ziwen Liu, Borui Zhan, Hong Chen, Jiamei Wang, Weixuan Zou, Huinan Xu, Ruitao Lu, Dongyao Ni*, Bernard Roizman* and Grace G Zhou*
Systemic administration of checkpoint inhibitors alone and especially concurrent with intratumoral administration of oncolytic herpesviruses (oHSV) has a major impact on cancer therapy marred by rare failures of healthy organs. Furthermore, tumors vary with respect to susceptibility to oncolytic effects of oHSV. Here we report the construction and properties of 3 families of oncolytic herpes simplex viruses expressing no immunomodulatory genes (T1 series), murine IL-12 (T2 series) or murine or human IL-12 and anti PD-1 antibody (T3 series). We report that insertion of the gene encoding PD-1 Ab significantly augmented the oncolytic activity of oHSV bereft of immunostimulatory genes (T1 series) or expressing IL-12 alone (T2 series). The T3 oHSV expressed IL-12, PD-1 Ab were restricted to the tumor bed whereas the induced IFN-γ accumulated to high levels both in tumor bed and in bl.. View More»
DOI:
10.35248/2471-9552.19.5.154