Immunotherapy: Open Access has released a research on Enhancement of Oncolytic Activity


Immunotherpay: Open access has released an article recently on Enhancement of Oncolytic Activity of oHSV Expressing IL-12 and Anti PD-1 Antibody by Concurrent Administration of Exosomes Carrying CTLA-4 miRNA by 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 from China. The article was in press of the Journal. The abstract of the above article was given below:


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 blood. Furthermore, the T3 oHSV was superior to systemic administration of IL-12 and antibody to PD-1. This report also shows that the oncolytic activity of T3 oHSV in a relatively resistant tumor was enhanced by concurrent intratumoral administrationof genetically engineered exosomes carrying miRNA targeting CTLA-4 checkpoint.


In this article the author reports on the properties of a family of novel oncolytic HSV (oHSV). The family consists of mutants without inserts, mutants incorporating mouse or human IL-12 alone or in addition murine or human genes encoding single chain antibody against PD-1 (PD-1 Ab). We also report on an adjunct therapy effective in tumors resistant to the oHSV. Recent advances in the studies led to the identification of nucleotide sequences of RNAs preferentially packaged into exosomes. We have used this information to construct miRNAs and package into exosomes that specifically target mRNAs encoding specific proteins [28-31]. In the studies reported here we targeted mRNA encoding the CTLA-4 checkpoint. The results suggest that the immunotherapy of MFC tumors was significantly enhanced by the concurrent inhibition of both PD-1 and CTLA-4 checkpoints.


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