City of Hope opened a first-in-human clinical trial for patients with recurrent glioblastoma. It represents the first trial to combine City of Hope’s chimeric antigen receptor (CAR) T cells that target IL 13Rα2 antigen common on brain tumor cells in combination with Opdivo, an anti-PD1 antibody, and Yervoy, also a checkpoint inhibitor that blocks the CTLA-4 protein.
A Deadly Cancer
Patients with recurrent glioblastoma (brain cancer) have few options and the condition rapidly turns deadly. Survival is about a year and only 5% live for more than 5 years.
The National Institutes of Health (NIH) have infused $3.3 million over 5 years to support this important study directly to the investigators including Behnam Badie, M.D., The Heritage Provider Network Professor in Gene Therapy and chief of City of Hope’s Division of Neurosurgery, and Christine Brown, PhD, City of Hope’s The Heritage Provider Network Professor of Immunotherapy as well a deputy director of City of Hope’s T Cell Therapeutics Research Laboratory. Gateway for Cancer Research has allocated $800,000 for the study as well. Of course, City of Hope’s underlying operational and infrastructure costs are involved.
The investigators will deliver CAR T cells that target IL 13Rα2 locally to the brain, by direct injection to the tumor site and through infusion into the ventricular system. The study will include 92 participants and will run until 2020.
According to their recent press release, City of Hope was the first to use this type of delivery for glioblastoma patients receiving CAR T treatment, as well as the first to investigate CAR T cells targeting IL 13Rα2. In the 2016 City of Hope produced a case study published in the New England Journal of Medicine outlining how a City of Hope patient’s brain cancer regressed by 7.5 months after receiving CAR T therapy to effectively attack cells with IL 13Rα2.
During the trial, the patients will receive the IL 13Rα2 CAR T cells weekly combined with nivolumab every other week. Patients on the experimental arm will additionally receive both Opdivo and Yervoy each dosed once 14 days prior to the start of combination therapy with CAR T cells plus Opdivo.
Bristol-Myers Squibb (BMS) Contributes to Product
BMS offers two products (nivolumab/Opdivo) and (ipilimumab/Yervoy) to support this advanced study. Opdivo is an immune checkpoint inhibitor that can prevent the PD-1 protein from doing its job, which is to suppress the immune system from fighting cancer. The goal is to put the PD-1 in check, allowing the immune system to better fight cancerous cells. Yervoy blocks the CTLA-4 protein in a similar way.
Opdivo has been approved by the Food and Drug Administration (FDA) for various cancers such as metastatic melanoma, nonsmall cell lung cancer, classical Hodgkin’s lymphoma, and head and neck cancer. Other clinical trials are underway. Yervoy is approved by the FDA for metastatic melanoma or in combination with Opdivo for renal cell carcinoma and colorectal cancer.
Behnam Badie, M.D., The Heritage Provider Network Professor in Gene Therapy and chief of City of Hope’s Division of Neurosurgery
Christine Brown, Ph.D., City of Hope’s The Heritage Provider Network Professor of Immunotherapy as well a Deputy Director of City of Hope’s T Cell Therapeutics Research Laboratory
Mustang Bio Connection
City of Hope licensed its patents associated with IL 13Rα2 CAR T cell therapy to publicly traded Mustang Bio Inc. (MBIO). The clinical-stage venture focuses on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors, and rare genetic diseases. Mustang Bio seeks out and acquires rights to advance technologies for research and develop. Some partnerships include the City of Hope, St. Jude Children’s Research Hospital, Fred Hutchinson Cancer Research Center Nationwide Children’s Hospital and Harvard University.
Founded in 2015, the venture became publicly traded during August 2017. Although publicly traded, Mustang Bio’s business model, like many research-based life science ventures, is fraught with risk. It could take several years before some of its portfolio therapies are commercialized—if ever. Thus, although publicly traded at $2.98 per share ($120.6m market cap) it recently completed a debt transaction of $20 million with Horizon Technology Finance. They have set up a cell processing center in Worcester, MA and this additional working capital support continued development of the gene and cell therapies there. Its’ pipeline exhibits hope for advanced treatments for deadly cancers should it make it through clinical trials with FDA approvals. The venture keeps its fixed labor overhead to a minimum with under 30 employees. Their MB-102/CD123 is farthest along toward commercialization according to CEO Licthman earlier in the year.
City of Hope
Founded in 2013, City of Hope is a leading biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. They are positioned as a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. Human synthetic insulin and numerous breakthrough cancer drugs are based on technology developed at the institution. City of Hope is a National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network. They have been the highest-ranked cancer hospital in the West based on U.S. News and World Report’s Best Hospitals: Specialty Ranking.