The hidden weapon hides within a patient’s own cells.
When someone is diagnosed with lymphoma or another blood cancer, chemotherapy is the best weapon to treat it. When it fails to rid the body of the cancer, or the cancer comes back, circumstances are bleak for patients.
But a group of doctors at Franciscan Health Indianapolis have found a potent weapon in genetically modified immune system cells used to treat some types of blood cancer.
"Having options in an otherwise very difficult-to-treat situation brings a lot of hope," said Dr. Luke Akard, a cancer specialist with the Indiana Blood & Marrow Transplantation program at Franciscan Health Cancer Center in Indianapolis. "Those patients were without a lot of other options."
The breakthrough treatment offers new hope for patients who otherwise would have few options in treating their lymphoma. The patient’s own immune system is modified to recognize unique proteins on lymphoma cells and potently kill cancer, ridding the body of existing cancer cells and protecting against recurrence.
Though only currently useful as a treatment in certain cases of lymphoma, the therapy holds promise for other cancers, Akard said.
"It’s been tested with multiple cancers, and the question becomes can you do a similar thing with other kinds of cancers. We know there are some unique proteins on other kinds of cancers. Could we target breast cancer, melanoma, lung cancer?" Akard said. "So far, it hasn’t been as successful, but it may just be a work in progress."
The technique is called CAR T-cell therapy, and has been approved by the Food and Drug Administration to treat diffuse large B-cell lymphomas. The cancer is a fast-growing disease that impacts the B-lymphocytes, a type of white blood cell that make antibodies to fight infections and are an important part of the lymphatic system.
Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma in the U.S. and worldwide, according to the Lymphoma Research Foundation. More than 18,000 people are diagnosed with the disease each year.
"There’s your standard chemotherapy that cures over half of people. In patients who relapse, some people will respond to another round of chemotherapy, and some people don’t," Akard said.
Relapsed patients who do respond are then treated with a high-dose chemotherapy regimen and an autologous transplant — their own blood forming stem cells are collected out of the body, then put back after the chemotherapy to replenish the patient’s blood cells.
But in others, the cancer holds on.
"We don’t have a lot of options for them, other than trying one recipe after another. Ultimately, the disease wins," Akard said.
The CAR T-cell therapy was developed for that group of patients. Cancer cells have a distinct group of proteins on their surface that are unique to the cancer. Researchers searched for a way to use those proteins to target a treatment. An antibody was developed 20 years ago that attached to a cancer cell, targeting it for the immune system.
By itself, that drug stops working over time in many cases, Akard said.
"So the idea was, could you take advantage of a target on the surface to bring immune cells to them? That’s what CAR T-cells are — trying to target cancer cells by bringing the immune cells to it to kill things it doesn’t like," he said.
The therapy starts by isolating, collecting and analyzing a patient’s T-cells, essential components of the blood used to fight disease and infection. Those cells are sent to a lab in California, which cultivates and grows those cells in controlled laboratory conditions. Using a technique known as a viral vector, a genetically engineered piece of DNA is implanted into the cells using a virus.
Within that DNA is an antibody that finds lymphoma, Akard said.
"The new gene allows that T-cell allows it to recognize and try to kill the target protein on the lymphoma," he said.
After technicians ensure that the T-cells are working properly in searching out cancer, the genetically engineered cells are sent back to Indianapolis to be reinserted into the patient’s body. The treatment works best with a three-day dosage of chemotherapy that suppresses the immune system, Akard said.
Then, the key is waiting for the cells to do their job in the patient’s body.
The technology is in its infancy, having only recently moved out of trial phase and approved for qualified patients by the FDA.
Akard has been the primary investigator of the clinical trial at the Indiana Blood & Marrow Transplantation Program, joined by his colleagues Dr. John Edwards, Dr. Anand Tandra and Dr. Michael Dugan. The trial started in 2016, and has been ongoing.
Since 2017, Franciscan Health Cancer Center has treated six patients using the treatment. The therapy is not perfect, but thus far, the treatment has shown to have a 30 to 50 percent success rate in removing all cancer from patients after 12 to 18 months.
"Still, in patients that don’t have any other therapy options, that’s better than anything else we have," Akard said.
