NFCR Translational Research: Brain Cancer
Developing New Treatment for Childhood Brain Cancer, Meduloblastoma
Cesare Spadoni, Ph.D., MBA University of London
In 2017, NFCR began support for the research of Dr. Cesare Spadoni, who lost his daughter to cancer and Mr. Ricardo Garcia, whose son is a cancer survivor. The need is great to develop treatments for those childhood cancers in dire need of effective treatments. Only four pediatric specific drugs gained approval in the last 20 years versus 200 for adults, due to the dismal financial investment for pediatric cancer-specific drugs.
NFCR’s support for the research discovery program for Medulloblastoma, a malignant childhood brain cancer, is strong. Medulloblastoma accounts for 20% of all childhood brain tumors and has high heterogeneity (caused by different genes) and a tendency to metastasize (spread). Ongoing research is identifying a lead compound that inhibits two targets (gene abnormalities or vulnerabilities) in the cancer – this will increase efficacy and reduce toxicity and resistance to the treatment. The research aims to select and characterize a preclinical candidate to be ready to enter into the pre-clinical phase in late 2022.
MULTI-ACTION GENE THERAPY FOR AGGRESSIVE
BRAIN CANCER, GLIOBLASTOMA (GBM)
Paul B. Fisher, M.Ph., Ph.D. Virginia Commonwealth University, Richmond, VA
A potential new therapy for GBM is Interleukin gene family member, IL/24, discovered by Dr. Paul Fisher. With NFCR support, his team showed IL/24 has robust anti-cancer actions in models of GBM and other solid tumors: 1) modulates the immune system, 2) inhibits formation of blood vessels, starving tumors of vital blood, and 3) sensitizes tumors to radiation, chemotherapy and immunotherapy, without toxicity in normal cells.
One of several ways to deliver IL-24 to tumors is through a common cold virus genetically reengineered by Dr. Fisher. Naming the treatment Cancer Terminator Virus (CTV), it houses and delivers IL/24 gene to only cancer cells throughout the body. IL/24 causes cancer cells to commit suicide (normal way cells die) and unleashes its other potent anti-cancer properties. Dr. Fisher is bringing CTV IL/24 gene therapy to clinical trials. Currently, with NFCR funding, CTV IL/24 gene therapy is advancing through pre-clinical research to apply for an Initial New Drug (IND) application from the FDA to treat GBM patients in a Phase 1 clinical trial.
New Inhibitor of Cancer Invasion and Metastasis into Healthy Tissue
Invasion of cancer cells into healthy tissue is a hallmark property of cancer cells in the aggressive brain cancer, GBM or glioblastoma. MDA-9/Syntenin is a pro-invasion and pro-metastatic gene discovered by Dr. Paul Fisher with NFCR funds. With leading-edge chemistry and drug design techniques, his team developed the drug, PDZ1i, to inhibit invasion and metastasis properties of MDA-9/Syntenin. The scientists are developing PDZ1i for clinical trials. PDZ1i shows profound “anti-invasive” and “anti-metastatic” activity in models of GBM and in liver, lung, pancreas, breast and prostate cancer and melanoma and neuroblastoma. PDZ1i works well with chemotherapy, radiation, or immunotherapy to kill cancer cells. Patients with hepatocellular cancer (HCC)—the main type of liver cancer, need effective treatments to save their lives. NFCR funds are advancing the required pre-clinical research of PDZ1i to apply for the IND (Investigational New Drug) application and gain FDA approval for a Phase 1 clinical trial for HCC patients. Success in the trial for HCC patients will facilitate future trials of PDZ1i treatment for GBM.
CLINICAL RESEARCH
GBM AGILE is an innovative clinical trial platform to accelerate the evaluation of new treatments for GBM. NFCR is a founding member a strategic partner with the Global Coalition for Adaptive Research (GCAR), the official sponsor of GBM AGILE. This uniquely designed platform has the ability to test multiple therapies at the same time against a common control (or standard of care). Currently, three arms of new experimental therapies are treating patients – giving patients hope for an effective treatment.
BASIC RESEARCH PROJECTS
Dr. Rakesh Jain a renowned expert in understanding the tumor’s abnormal microenvironment, previously discovered that an imbalance of vessel growth in tumors results in leaky blood vessels (edema), lack of oxygen and immunosuppression. His research is now determining why a new revolutionary immunotherapy is not effective in GBM. In models of GBM, his team discovered the abnormal vessels limit the immune system’s T cells to kill tumors. Normalizing these vessels has high potential to improve treatment outcomes and increase survival in GBM patients.
