For the past several decades, research teams have spent countless hours and funds trying to learn more about cancer and discover new ways to treat it. And although many new insights have been gleaned, cancer still remains a very difficult-to-treat disease. Despite innovative immunotherapy treatments that do sometimes show success, tumors have their own powerful ways of evading the system that was designed to attack them. Sadly, only a small number of cancer patients actually respond to the therapies, and many experience negative side effects.
But a research team from the Institute for Molecular Engineering at the University of Chicago believes they have come up with a new way to deliver immunotherapy directly to the tumors. This method could help to reduce side effects and make the treatments more effective.
How does immunotherapy work?
Immunotherapy works by aiding the immune system in detecting and fighting off cancerous cells. Although the immune system is inherently designed to ward off foreign invaders, cancer finds ways to evade its attack. The immune system uses checkpoints — or molecules on immune cells that need to be turned on in order to begin an immune response — to determine whether a cell is foreign or familiar. Cancer finds a way to take over these checkpoints to make sure it goes undetected by the immune system.
Immunotherapy treatments are focused on overcoming this issue. One form of treatment is a drug called a checkpoint inhibitor. It functions by getting in the way of proteins in order to allow immune cells to see and destroy cancer. Another examples is a therapy called interleukin (IL)-2, which is a protein created by white blood cells that stimulates the growth of immune cells. This drug helps to enhance the immune system’s ability to attack cancer.
Both of these therapies, along with some others, have proven successful in many patients with certain kinds of cancer. But they have also failed several patients, causing harmful side effects and showing no impact on tumors.
A new immunotherapy target could help to remedy some of these issues.
Jeffrey Hubbell, the Eugene Bell Professor in Tissue Engineering, co-authored this new research that recently appeared in Science Translational Medicine. He collaborated with Melody Swartz, the William B. Ogden Professor, and postdoctoral fellow Jun Ishihara. The team set out to find another way to deliver immunotherapy drugs that more directly reached the tumors.
The unique approach developed by these researchers involves collagen, one of the most abundant proteins in the body. Collagen is especially present in tumors. The team thus thought that if there was a way to administer immunotherapies directly to the collagen in the tumor, it could increase efficacy and reduce side effects.
In order to make this happen, the researchers combined the checkpoint inhibitor drugs with the IL-2 therapy and bound them to a blood protein that binds to collagen in areas of vascular injury. This causes blood to congeal and seal the injury. Tumors are replete with leaky blood vessels, so theoretically, the protein would identify those vessels as injuries and bind to them, which would administer therapies directly into the collagen within the tumor.
The therapy was given to patients intravenously, which also allows it to identify and treat metastatic tumors that may even be unknown to the patient and their doctor.
The study’s initial findings were positive. They showed that the combination of CPI and iL-2, given with their technique, destroyed breast tumors in 9 out of 13 animal models. This is in comparison to only one out of 13 destroyed when given the drug without the collagen-seeking protein.
Their protocol also inhibited the growth of melanoma and colon tumors and decreased liver and lung toxicity from the drugs, which could mean fewer side effects in patients.
According to Ishihara, the research may have “create[d] a comfortable immunotherapy for cancer patients . . . one that improves both safety and efficacy.”
How can patients get access to this treatment protocol?
Hubbell believes that “this therapy could be relevant to many solid tumors.” The team is hoping to move the study forward to clinical trials to see how patients who previously did not respond to immunotherapies might now respond.