1. Oncolytic herpes simplex virus type-1 expressing IL-12 efficiently replicates and kills human colorectal cancer cells
- Author
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Ladan Teimoori-Toolabi, Mohammad Sadegh Shams Nosrati, Nasrin Haghighi-Najafabadi, Farzin Roohvand, and Kayhan Azadmanesh
- Subjects
Oncolytic Virotherapy ,medicine.medical_treatment ,Immunotherapy ,Herpesvirus 1, Human ,Biology ,medicine.disease_cause ,Microbiology ,Virology ,Interleukin-12 ,Virus ,Oncolytic virus ,Infectious Diseases ,Herpes simplex virus ,Cell culture ,Interleukin 12 ,medicine ,Leukocytes, Mononuclear ,Cytotoxic T cell ,Humans ,Cytotoxicity ,Colorectal Neoplasms - Abstract
An increasing attitude towards oncolytic viruses (OVs) is witnessed following T-VEC's approval. In this study, we aimed to delete ICP47 and insert IL-12 in the ICP34.5 deleted HSV-1 backbone to improve the oncolytic properties and provide an immune-stimulatory effect respectively. The wild-type and recombinant viruses infected both cancerous, SW480 and HCT116, and non-cancerous, HUVEC, cell lines. Green-red Δ47/Δ34.5 was constructed by replacing ICP47 with GFP. Both ICP34.5 copies were replaced by hIL12. Cytotoxicity and growth kinetics of Δ47/Δ34.5/IL12 and Δ47/Δ34.5 were comparable to the wild virus in the cancerous cells. Δ47/Δ34.5/IL12 was able to produce IL12 in the infected cell lines. INF-γ production and PBMC proliferation were observed in the PBMCs treated with the lysate of Δ47/Δ34.5/IL12 infected cells. These results demonstrated that Δ47/Δ34.5/IL12 was competent in taking advantage of the cytotoxic effect of HSV-1 plus immune-stimulatory characteristics of IL-12.
- Published
- 2021