FDA Clears Colorado University Anschutz’ CAR T-Cell Trial for Colorectal Cancer
The investigators will evaluate a dual-target CAR T-cell therapy designed to attack B7-H3 and IL-8 in adults and children with advanced solid tumors.
Key Points
- The FDA has cleared a CU Anschutz clinical trial of an experimental CAR T-cell therapy for advanced solid tumors.
- The therapy targets B7-H3 on cancer cells and the IL-8 pathway associated with tumor growth and spread.
- The trial will initially assess safety and the engineered cells’ ability to attack cancer in adults and children who have exhausted standard treatments.
Colorado University Anschutz investigators have received FDA clearance to test an experimental chimeric antigen receptor (CAR) T-cell therapy in adults with advanced colorectal cancer and children with solid tumors who have exhausted standard treatment options.
CU Anschutz developed the therapy, and the Gates Biomanufacturing Facility will manufacture it. It is designed to target B7-H3, a protein found on most colorectal tumors, and IL-8, a protein involved in tumor growth, inflammation and cancer spread.
Christopher Lieu, MD, professor of medical oncology at CU Anschutz and associate director of clinical research at the CU Anschutz Cancer Center, will lead the trial.
“This is a very different way of thinking about how we treat cancer,” said Michael Verneris, MD, professor of pediatric oncology at CU Anschutz and program co-leader of Tumor-Host Interactions at the CU Anschutz Cancer Center. “We wanted to find targets that are present across many different cancers rather than developing a therapy that would only apply to a small number of patients.”
A Dual-Target Approach
CAR T-cell therapy involves collecting a patient’s T cells and genetically modifying them to recognize and attack cancer. The engineered cells are expanded and returned to the patient.
CAR T-cell therapies have been effective against some blood cancers, including leukemia and lymphoma. Solid tumors have proved more difficult to treat because suitable targets must be abundant on cancer cells but limited on healthy tissue. Engineered immune cells must also overcome the defenses surrounding solid tumors.
B7-H3 is being studied as a cancer target because it is found on many colorectal tumors. The CU Anschutz therapy also targets IL-8, which is part of a pathway that can support tumor growth and spread. Researchers hope this combination will help the engineered cells attack solid tumors more effectively.
“Chemotherapy extends survival and helps cure people,” Lieu said. “At the same time, it’s like dropping an unguided bomb on a disease. Maybe you hit your target, but you are going to do a lot of collateral damage.”
The therapy has shown efficacy in animal models. Investigators now want to determine whether it can produce durable responses in people.
“Immunotherapy gives us the opportunity to direct the immune system toward the cancer and potentially produce a much more durable response,” he said.
Addressing Limited Treatment Options
Colorectal cancer rates among adults younger than 45 have increased substantially over recent decades. Researchers are still investigating the reasons for this trend.
Patients with advanced colorectal cancer have increasingly limited options after standard therapies stop working. Only a small percentage of patients with colorectal and other gastrointestinal cancers qualify for certain immunotherapies because those treatments depend on specific tumor biomarkers.
B7-H3 is present in a larger proportion of colorectal cancers. The researchers hope this could eventually make the approach relevant to more patients. The initial trial must first establish whether the therapy is safe and can attack cancer in people.
“Given the number of patients we are seeing, we need new approaches,” Lieu said.
If the approach proves successful, it could later be studied in other cancers involving the same pathways, including some breast, lung and ovarian cancers.
From Development to Clinical Testing
The Gates Biomanufacturing Facility will produce the engineered cells for the trial. Its location near CU Anschutz, Children’s Hospital Colorado and UCHealth University of Colorado Hospital allows research and manufacturing teams to work alongside the clinical investigators.
“The whole spectrum is right here,” Verneris said. “If we didn’t have the Gates Institute, we wouldn’t be able to make our own cells. This could have remained an interesting idea. Instead, it has become a clinical trial that could have a real impact on patients.”
“These trials cost a lot of money,” Verneris said. “Private philanthropy is what makes it possible to take an idea like this and move it into patients. We are incredibly grateful to the donors who have helped make this possible.”
The trial is expected to begin in December.
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