By Kim Polacek, APR, CPRC - June 03, 2020
Chimeric antigen receptor T-cell therapy, or CAR T, has given leukemia and lymphoma patients who have failed multiple treatments a new option. CAR T is a cellular immunotherapy that uses a patient’s own T cells to fight their cancer. T cells are removed from the body through a process called apheresis and are sent to a lab where they are genetically modified, adding a receptor that acts as a GPS allowing the T cells to find and kill cancer cells once infused back into the body.
CAR T has been so successful, clinical trials are underway to determine if the therapy can be used to treat other types of cancer. Researchers are also investigating if the cellular immunotherapy can be used to treat diseases other than cancer. One such study, launched by Dr. Marco Davila, a medical oncologist at Moffitt Cancer Center, and published in the Journal of Clinical Investigation, shows the benefit of using CAR T to prevent and/or treat graph-versus-host disease (GVHD), a potentially deadly complication that can occur following a stem cell transplant.
Stem cell transplants are a common treatment for patients with certain cancers of the blood or bone marrow. GVHD happens when cells from the donor attack the recipient’s tissue and organs. Treatment for GVHD involves suppressing the immune system, putting already immunocompromised cancer patients at risk for further complications. These GVHD therapies can also reduce the ability of stem cell transplants to cure the patient’s cancer.
"Our common goal with stem cell transplantations is to prevent GVHD from happening, but if it does occur, we want a way to treat it without adverse reactions or without reducing the ability of the transplant to cure our patients’ cancer."- Dr. Marco Davila, Medical Oncology & Medicial Director of Cell Therapies
“Our common goal with stem cell transplantations is to prevent GVHD from happening, but if it does occur, we want a way to treat it without adverse reactions or without reducing the ability of the transplant to cure our patients’ cancer,” said Davila.
Davila and his team, which included researchers from Masonic Cancer Center in Minnesota, thought the next generation of cellular immunotherapy, CAR T, could be the answer to treat a major complication of one of the first forms of cellular immunotherapy, stem cell transplantations. Previous studies in mice have shown that targeting CD83, a protein that is expressed on immune cells, can prevent GVHD. They wanted to determine if using CAR T to target and kill immune cells expressing CD83 could, in turn, prevent and also treat GVHD. They tested their theory through a series of lab experiments using mouse and human cells.
“Our lab studies confirmed that CD83 CAR T therapy has the potential to prevent and treat GVHD by killing the immune cells that are destroying the host tissues,” said Davila. “More importantly, the treatment works without compromising the immune system.”
Davila said the next step would be to launch a clinical trial to better determine the treatment’s efficacy for GVHD. He also added that targeting CD83 with CAR T cells can be applied to treat other diseases of overactive immune cells attacking tissues, such as autoimmune diseases. There is also a possibility that CD83 CAR T could be used to treat certain cancers. “We demonstrated this specific cellular immunotherapy has the ability to kill myeloid leukemia cells, so we would like to design a study to determine if it can be used for the treatment of acute myeloid leukemia,” he said.