Brain Tumors Research

Glioblastoma (GBM) Therapeutics Network (GTN)

Principal Investigators: Jana Portnow, M.D., and Behnam Badie, M.D.

Overall Goal

The overall goal of the Glioblastoma (GBM) Therapeutics Network (GTN) U19 grant awarded to City of Hope®, is to develop superior treatments for patients with GBM, the most common and aggressive primary brain tumors in adults. Effective treatments remain elusive and patients are rarely cured with standard therapies. This GTN U19 grant will fund a unique combination of approaches designed to significantly advance the treatment of patients with GBM by addressing tumor heterogeneity, blood-brain barrier penetration, and the immunosuppressive GBM tumor microenvironment. The three proposed research projects will translate therapeutic agents from preclinical development, through IND-enabling studies, and into Phase I clinical studies in adult patients with GBM. Each project is based on novel molecular preclinical studies with small-molecule inhibitors and immunomodulatory agents that use signature-guided assessment and treatments.

Specific goals of the projects are listed below.

Project 1: Develop and clinically test an engineered oncolytic herpes virus expressing a full- length anti-CD47 monoclonal antibody for treatment of GBM.

Project 2: Develop and clinically test a novel approach to enhance the efficacy of anti-GBM immunotherapies administered peri-operatively.

Project 3: Develop and clinically test a molecular “signatures of vulnerability” guided treatment of GBM.

In addition, this U19 grant will help researchers investigate strategies that will address major barriers in drug development by incorporating two innovative research tools: 

1. Intracerebral microdialysis to rationally select appropriate systemically administered therapies for testing in GBM patients 

2. Next-generation exome and transcriptome sequencing to identify molecular “signatures of vulnerability” that can guide appropriate patient selection for clinical trial enrollment

These analytical capabilities will enable us to quantify CNS drug penetration and dissect genomic heterogeneity in tumor and stromal cells in the proposed clinical trials. Also, two of the proposed projects leverage City of Hope’s good manufacturing practice (GMP) facilities to manufacture biological agents and small molecules that will be tested in adult GBM patients for the first time. 

In summary, the innovative projects and shared resources supported by this grant combine our strengths in basic, translational and clinical research in a highly collaborative setting that promotes the sharing of ideas, results, resources, and clinical populations to develop effective treatments for GBM. If successful, data generated by these studies have the potential to transform the treatment of adult GBM patients by introducing new agents that circumvent tumor heterogeneity and immunosuppression.

Brain Tumor Research Labs