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Viral Oncolytic Therapeutics for Neoplastic Meningitis
Annual rept. 1 Jul 2011-30 Jun 2012
MASSACHUSETTS GENERAL HOSPITAL BOSTON
Pagination or Media Count:
Neoplastic meningitis is a severe complication of breast cancer for which there is no curative treatment at present. The project aims to develop a novel, safe and efficient therapy for neoplastic meningitis HSV-1 oncolysis therapy. For the first year of the award period we have propagated the HSV-1 replication conditional mutant hrR3 with burst assays and generated three different virus preparations to establish viral titers of 1x107, 1x108 and 1x109 pfuml. The virus titers were determined by plaque assays performed on vero mono-layers. These virus titers will be used to study fractionated viruses particles. In addition we have commenced on additional work that will help study the disease progression by molecular imaging. In anticipation of establishing a mouse model of meningeal metastasis we have developed stable breast cancer cell lines that express bioluminescence and fluorescence markers for in vivo molecular imaging. Three cell lines human breast cancer cell lines SkBr3 and MDA-231, and the mouse breast cancer 4T1 were transfected to express renilla luciferase RLuc and mCherry, both driven by the CMV promoter. Clones that were resistant to puromycin were selected to establish stable cell lines. These stable cell lines have been tested for i the replication efficiency HSV-1, and ii their sensitivity to the HSV-1 oncolysis with in vitro bioluminescence. Based on these preliminary data we anticipate proposing the use of one of the cell lines to establish a mouse model of meningeal metastases. We will in due course approach DOD for approval of the animal protocol.
APPROVED FOR PUBLIC RELEASE