Development of a Novel Model for Exploring the Role of Regulatory T-cells in Oncolytic HSV Cancer Therapy
Year: 2011
Type: article
Abstract: Cancer remains one of the scourges of modern life despite our radical advances in medical technology and treatment.The need for improved therapies is apparent in the pediatric sarcoma population, including patients with rhabdomyosarcoma, who have a five-year survival of less than thirty-percent when diagnosed with metastatic disease.One emerging anti-cancer approach is the use of oncolytic viruses.Viruses derived from wild-type herpes, but possessing genetic modifications to alter their virulence and render them safer, have been tested in clinical trials and show promise as an anti-cancer treatment.The use of any oncolytic agent is likely impacted by the functions of the patient's immune system; in theory, the host could mount a beneficial attack against the cancerous cells, or a harmful attack against the treatment agent itself, the latter of which would be expected to limit the anti-cancer activity of oncolytic viruses.I sought to develop a suitable model for exploring the interplay between the tolerogenic regulatory T-cells and the anti-viral and anti-tumor immune effector cells, which could be used to determine their role in the presence of oncolytic virus treatment.To this end, I required a tumor model in animals which possess an intact adaptive immunity for this study, yet human HSV replication is generally attenuated in mouse cells, in contrast to human tumor cells.Thus, I first screened mouse tumors for susceptibility to HSV infection.I used a mouse genetically susceptible to rhabdomyosarcoma due to expression of the hepatocyte growth factor/scatter factor transgene in the INK4a/ARF-/-background.I tested several cell lines derived from tumors to determine their ability to be killed by and support the replication of an oncolytic herpes simplex virus, rRp450.I also tested their tumorigenicity in standing by me through all adversity and providing continued support and advice, as well as, sacrificing their extremely valuable time to hear my ramblings and ideas.
Author: William H. Baird
Institution: University of Cincinnati
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2596305292