# Pre-Clinical Vector Production Core

> **NIH NIH P01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $155,559

## Abstract

PROJECT SUMMARY – CORE 1
 Glioblastoma (GBM) remains amongst the most deadly and difficult to treat forms of brain tumors. We have
been interested in using oncolytic viruses, based on herpes simplex virus type 1 (HSV-1), as a selective tumor-
killing virus. Considerable effort in the vector development resulted in the engineering of oncolytic HSV vectors
(oHSV) such as rQNestin34.5 and KGN-4:T124 that are non-toxic for normal cells, yet capable of selective
replication in GBM tumor cells. Both of these oHSV will enter into Phase-I clinical trials within 2017. The overall
hypothesis of the Program Project is to test newly engineered armed versions of these oHSV in immune
competent mouse models. In order to effectively use oHSV in animal tumor models it is necessary to propagate
and purify oHSV to high titers. Efforts in process development have resulted in scalable systems capable of
manufacturing rQNestin34.5, KGN-4:T124 and other oHSVs.
 My laboratory has spent considerable time developing refined and novel methodologies to improve virus
production, purification and quality assessment to provide high quality vector stocks with dramatically reduced
levels of protein and DNA contaminants (>99% removal) that can contribute to toxicity, immunity and
biodistribution as well as confound in vivo efficacy studies. Our efforts in process development have resulted in
scalable systems capable of manufacturing these vectors for pre-clinical efficacy and safety testing resulting in
a 10 to 30-fold increase in overall virus yield and a corresponding 60-fold increase in concentration of
the virus. The Core is in the unique position of being one of a few sites for oHSV virus vector production,
purification and quality assessment testing. This extensive expertise along with our prior collaborative interaction
consisting of 33 oHSV vector stocks produced and distributed to the 4 Projects since 2012, supports the
overall success of the role of the Pre-Clinical Vector Core in the current proposal.
 The primary goal of the Core 1, that received a superior rating when the P01 was reviewed last, is to provide
large quantities of GLP-grade concentrated and purified oHSV vectors: (i) rQNestin34.5 and armed derivatives;
and (ii). KGN-4:T124 and armed derivatives to each of the 4 projects. The oHSV Pre-Clinical Vector Core will
work with the projects to provide optimal vector quantity and purity while providing the support necessary to
successfully exploit the available technology. We will continue to refine our production, purification and
assessment systems. Should any of the engineered oHSV vectors tested in the projects prove efficacious, the
Core would provide support to cGMP facilities for transfer of the production/purification technology of large-scale
oHSV manufacture for possible Phase-I human clinical trials.

## Key facts

- **NIH application ID:** 10251087
- **Project number:** 5P01CA163205-09
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** WILLIAM F. GOINS
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $155,559
- **Award type:** 5
- **Project period:** 2013-02-07 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10251087

## Citation

> US National Institutes of Health, RePORTER application 10251087, Pre-Clinical Vector Production Core (5P01CA163205-09). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10251087. Licensed CC0.

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