A novel oncolytic herpes simplex virus armed with the carboxyl-terminus of murine MyD116 has enhanced anti-tumour efficacy against human breast cancer cells.

A novel oncolytic herpes simplex virus armed with the carboxyl-terminus of murine MyD116 has enhanced anti-tumour efficacy against human breast cancer cells. Oncol Lett. 2018 May;15(5):7046-7052 Authors: Cheng L, Jiang H, Fan J, Wang J, Hu P, Ruan Y, Liu R Abstract Oncolytic herpes simplex virus-1 (oHSV-1) vectors are promising therapeutic agents for cancer. The deletion of the γ34.5 gene eliminates the neurovirulence but attenuates virus replication at the same time. The carboxyl-terminus of protein phosphatase 1 regulatory subunit 15A (also known as MyD116/GADD34) is homologous to that of γ34.5; hence, it may substitute for γ34.5 to enhance the replication and cytotoxicity of the virus. To investigate whether the C-terminus of MyD116 can enhance the anti-tumour efficacy of G47Δ on human breast cancer cells, a GD116 mutant was constructed by inserting a γ34.5-MyD116 chimaera into the G47Δ genome using a bacterial artificial chromosome and two recombinase systems (Cre/loxP and FLPE/FRT). A GD-empty mutant containing only the cytomegalovirus sequence was also created as a control using the same method. Next, the replication and cytotoxicity of these two virus vectors were evaluated in breast cancer cells. Compared with the GD-empty vector, GD116 possessed an enhanced replication capability and oncolytic activity in MCF-7 and MDA-MB-231 cells. On the fifth day after infection with GD116 at MOIs of 0.01 and 0.1, 49.2 and 82.8% of ...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research