PROJECT SUMMARY – CORE 2 Oncolytic herpes simplex virus (oHSV) based therapeutics represent a promising and novel treatment approach for glioblastoma (GBM), which still has no effective conventional or targeted therapeutics. However, significant barriers exist to optimizing oHSV therapy and the research of the Core and Program are designed to gain knowledge that will allow improved designed and effectiveness of these agents. To achieve this the Glioblastoma Biorepository Core (Core 2) will provide investigators and all projects centralized access to authenticated resources essential to the planned experimental studies. These include human and mouse glioblastoma samples, associated clinical and genomic data, cell lines, and xenografts. The Core will also offer professional neuropathology and immunopathology expertise useful in interpretation of experimental results and their clinical relevance. These services will greatly aid the program's investigations of mechanisms of resistance to oHSV therapy and discovery of new approaches to improve oHSV treatment as single agent or in combination with other treatments (e.g. checkpoint inhibitors). The Biorepository Core will achieve these goals through three specific aims that support all the Projects. Aim 1 is to generate and maintain a repository of consented glioblastoma samples and data. This will include sample triage by Neuropathologists and distribution from the clinical trial of rQNestin34.5 planned in Project 2 and utilized by Projects 2, 3 and 4 (tissue and blood). Aim 2 is to create and distribute glioblastoma patient derived cell lines (PDCL) and xenografts (PDX). These will be created from the rQNestin34.5 trial patients as well as non-trial GBM patients. The Core will also provide and authenticate mouse syngeneic glioma models (e.g. GL261-N4, CT2A, 4C8) utilized by all Projects. Aim 3 is to provide expert neuropathology, immunopathology, and molecular analysis of glioblastoma tissues and models. This includes genomic sequencing (e.g. EGFRvIII in Project 1, RNA expression to characterize targets relevant to oHSV trafficking and effects (e.g. Nestin Project 2, activated NOTCH Project 3), and multiplex co-localization studies of tissue samples for immune cell markers of lymphocytic, NK-cell (Project 4), and macrophage populations (e.g. PD1, PDL1, CD8) in collaboration with the DFCI Center for Immunooncology. In total the studies planned will facilitate centralized and efficient administration of resources and specialized expertise required to achieve the ambitious goals of the Program and advance the field of oHSV therapeutics for glioma and other cancers.