“Here at Cleveland Clinic, in addition to the number of patients we have and our clinical expertise, we also have world-renowned scientists that are designing the next and greatest therapies for us to deliver,” says John Molina, MD, EdM.

John Molina, MD, EdM

Jos Melenhorst, PhD

Co-Investigator

Celine Gregoire, MD, PhD

Co-Investigator

Cleveland Clinic Cancer Institute

Leukemia

Pilot Grant

Enhancing CAR T-cell Therapy to Better Treat Patients With CLL

Chronic lymphocytic leukemia (CLL), a type of blood cancer most common in adults, is treatable but not curable. Chimeric antigen receptor (CAR) T-cell therapy is an innovative treatment that utilizes a patient’s own T-cells to fight cancer cells. Currently, it is the best treatment for patients with CLL, but it needs to be improved.

CAR T-cell therapy relies on the patient’s body having enough functional T-cells that are capable of eliminating tumor cells. The problem is that many CLL patients do not have enough of these highly functional cells. John Molina, MD, EdM, Jos Melenhorst, PhD, and Celine Gregoire, MD, PhD, are examining how they can modify the existing cells within the body by using current therapies and then deciding when the best time is to collect these T-Cells to give them back to patients.

“This project is about finding that perfect time and amount of therapy and types of therapy we should give that will help us create a better CAR T-cell product in order to have a curative approach to this cancer in the future,” says Dr. Molina.

Timing is everything as collecting T-cells too early can hinder their performance. The team is looking at the potential hurdles in the engineering of patients’ immune cells.

“The challenge particularly in CLL is that there is an overabundance of tumor cells which makes it really hard to get even enough T-cells for the therapy,” says Dr. Melenhorst. “Also, because of this high abundance, it has produced an immune-suppressed environment in patients’ bodies.”

By studying current treatments, Dr. Molina, Dr. Melenhorst and Dr. Gregoire are hoping to improve patient outcomes. “The idea is to take patients samples, analyze what’s working and not working in patients, understand the differences and try to see how we can make the results better for all patients,” says Dr. Gregoire.

“What we can do here is take what we’ve learned from our patient experiences and outcomes, go to the laboratory, have new ideas, make modifications and then bring them back to the clinic,” says Dr. Molina. “It’s truly a bench-to-bedside effort at Cleveland Clinic.”