The experimental CAR T-cell therapy was developed by researchers at CU Anschutz and will be manufactured at the campus' Gates Biomanufacturing Facility. The cells are designed to attack two targets associated with cancer: B7-H3, a protein found on most colorectal tumors, and IL-8, a protein that helps promote tumor growth, inflammation and the spread of cancer.
If successful, the approach could eventually be tested against other cancers in which these pathways play a role, including some breast, lung and ovarian cancers.
"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."
Christopher Lieu, MD, professor of medical oncology at CU Anschutz and associate director of clinical research at the CU Anschutz Cancer Center, is leading the trial.
A two-pronged approach
CAR T-cell therapy involves collecting a patient's T cells, a type of immune cell, and genetically modifying them so they can recognize and attack cancer. The engineered cells are then grown in large numbers and returned to the patient.
CAR T-cell therapies have produced remarkable results in some blood cancers, including leukemia and lymphoma. But developing CAR T-cell treatments for solid tumors such as colorectal cancer has proved much more difficult.
One challenge is finding a target that is abundant on cancer cells but limited on healthy tissue.
B7-H3 is attractive because it is found on many colorectal cancers. Researchers at several institutions are investigating B7-H3 as a potential cancer target, but the CU Anschutz therapy takes an additional step by simultaneously targeting IL-8, which is part of a pathway that can help tumors grow and spread.
The researchers hope the combination will give the engineered cells a better chance of overcoming the defenses of solid tumors.
"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."
He's hoping this therapy, which has proven effective in animal models, will produce longer results. Not two months or four months but years.
"Immunotherapy gives us the opportunity to direct the immune system toward the cancer and potentially produce a much more durable response," he said.
An urgent need for new treatments
Colorectal cancer is increasingly affecting younger adults. Rates of colorectal cancer among people under 45 have risen substantially over the past several decades, while researchers continue to investigate the reasons behind the trend.
For patients with advanced colorectal cancer, treatment options become increasingly limited when standard therapies stop working.
"Given the number of patients we are seeing, we need new approaches," Lieu said.
Currently, only a small percentage of patients with colorectal and other gastrointestinal cancers are eligible for certain forms of immunotherapy because those treatments require specific tumor biomarkers. Because B7-H3 is present in a much larger proportion of colorectal cancers, the researchers hope their approach could ultimately be applicable to more patients.
But the first step is determining whether the therapy is safe and whether it can effectively attack cancer in people.
From laboratory to clinical trial
The trial highlights the innate advantages of CU Anschutz – home to a university, Children's Hospital Colorado, UCHealth University of Colorado Hospital and the Gates Biomanufacturing Facility all within easy walking distance of each other. This unique positioning allows researchers to seamlessly move their work from an idea to a laboratory experiment to a clinical trial.
"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."
Philanthropic support has played an important role in advancing the therapy toward clinical testing.
"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.
About the University of Colorado Anschutz Medical Campus
The University of Colorado Anschutz is a world-class academic medical campus leading transformative advances in science, medicine, education, and patient care. The campus includes the University of Colorado's health professional schools, more than 60 centers and institutes, and two nationally ranked independent hospitals – UCHealth University of Colorado Hospital and Children's Hospital Colorado – which see nearly three million adult and pediatric patient visits each year. Innovative, interconnected and highly collaborative, CU Anschutz delivers life-changing treatments, exceptional patient care and top-tier professional training. The campus conducts world-renowned research supported by $890 million in funding, including $762 million in sponsored awards and $128 million in philanthropic gifts for research.
Based at CU Anschutz, Gates Institute is a premier translational research institute with biomanufacturing capabilities that enables the development of life-saving treatments for a host of diseases at unmatched speed and scope. The institute brings together researchers and clinicians who specialize in regenerative, cell and gene therapies, accelerating their discoveries from concepts to cures.
Contact: David Kelly, University of Colorado Anschutz [email protected]
SOURCE University of Colorado Anschutz
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