Dr. Melissa Johnson of the Sarah Cannon Cancer Center in Nashville, TN talks to us about a multi-center clinical trial utilizing engineered t-cell therapy similar to CAR-T but better known as TRuC-T therapy (stands for TCR Fusion Construct T cells). While CAR-T cell therapy engineers the patient’s own T-cells with chimeric antigen receptors (CARs), Truc-t therapy engineers T-cell receptors (TCRs). Dr. Johnson is a thoracic medical oncologist and is the program director of Lung Cancer Research at Sarah Cannon Cancer Center.
What is a CAR-T cell?
CAR-T cells use a patient’s immune system against a tumor. Put simply, this therapy consists of attacking tumor cells with a patient’s own genetically engineered T cells. Usually, through this process, a patient’s T cells are trained to recognize mesothelin, a protein heavily expressed by certain types of mesothelioma. As a result, the newly engineered T-cells will attack mesothelin, and thus the mesothelioma tumor, when reintroduced into the patient.
What is TRuC-T therapy and how it is different from CAR-T therapy?
To simplify an extremely complex process, while the CAR-T cell therapy engineers one type of receptor (the chimeric antigen receptor) to recognize the antigen (mesothelin), the TRuC-T therapy fuses the full receptor domain onto the T cell for the same purpose.
How are the cells taken out of the patient’s body?
Cells are removed by reverse blood cell transfusion, first withdrawing blood then separating plasma from the blood (apheresis) and isolating white blood cells from it. This process lasts about four hours. The white blood cells are then frozen down and shipped to the lab to begin the process of teaching them to recognize the mesothelin receptor.
The process of the apheresis itself is widely used in other applications and is deemed very safe. Following the procedure, patients are not at an increased risk of infection or anemia because the cells removed are just a small fraction of a patient’s available white cells.
Process of re-introduction of engineered cells
Before returning the white blood cells to the patient, doctors tamp down the rest of the patient’s immune system with low dose chemotherapy to minimize the risk of the immune system destroying so the newly engineered white blood cells. can do what they’ve been instructed to do in the body.
“We don’t want a patient’s immune system to attack the newly engineered white blood cells and get rid of the very cells we’ve worked hard to make,” Dr. Johnson said.
Some known side-effects of chemotherapy can include anemia or thrombocytopenia, both manageable. At Sarah Cannon Cancer Center, patients are admitted to the hospital two days after they finish their chemotherapy to receive their T cells back. During this process, doctors look for fever, low blood pressure, and a decreased oxygen count as signs that the immune system has been activated. If all goes well, the patient will leave the hospital.
After the procedure, patients are asked to stay within one hour of the medical center in case of infection during the first month. The period of about a month until white blood cells go back to normal is when patients are at risk of infections.
Lodging options
The American Cancer Society’s Hope Lodge is often available near major cancer centers. Patients can work with their oncology nurse or social worker to apply. The Sarah Cannon Cancer Center in Nashville also has several relationships with nearby hotels that offer shuttle service to the center and back. Patients can apply for financial assistance to help with their lodging and travel costs through the Mesothelioma Applied Research Foundation’s Patient Travel Grant Program.
Does health insurance cover these treatments?
Therapies are paid for with a combination of private insurance and research grants. For the most part, the Sarah Cannon Cancer Center can bill the insurance company for everything that is considered standard of care, like lab visits, scans and doctors’ visits. Anything that is specific to the clinical trial is paid for by the company sponsoring the trial. Pleural and peritoneal patients both qualify for the trial, and they are not automatically disqualified if they’ve had prior immunotherapy.
Our sponsors
MesoTV is a program by the Mesothelioma Applied Research Foundation. This program is made possible by our generous sponsors: Maune Raichle Hartley French & Mudd, LLC (MRHFM); Belluck & Fox; Bristol Myers Squibb; Novocure; Merck; The Gori Law Firm; Early Lucarelli Sweeney & Meisenkothen.
