Research News

Two researchers under the mentorship of Cleveland Clinic’s Jos Melenhorst, PhD, have earned top honors from the American Society of Hematology (ASH) for cancer immunotherapy research projects aimed at reducing CAR T-cell therapy’s cost and improving its outcomes. Beatriz Coutinho de Oliveira, PhD, and Arun K. Arunachalam, MBBS, MD, received ASH Abstract Achievement Awards recognizing their research projects as among the best of the thousands of projects presented at the Society’s 2025 conference.  

 

CAR T-cell therapy, short for chimeric antigen receptor T-cell therapy, is a new treatment for certain blood cancers that isolates a patient’s own immune cells from their blood.  The cells are then genetically engineered and tailor-made to fight the patient’s specific cancer. The powered-up cells are infused back into the patient’s bloodstream, where they act as a “living medicine” that persists and replicates within the body to continually find and destroy cancer cells. 

When it works, CAR T-cell therapy has incredible cure rates that are worth the therapy’s potential side effects. However, engineering CAR T cells is a complex process that can cost hundreds of thousands of dollars. If the treatment doesn’t work, there can be an enormous financial and emotional toll.  

Dr. Arunachalam, a physician-scientist from Christian Medical College in Vellore, India, temporarily left his clinical practice to train under Dr. Melenhorst at Cleveland Clinic. Dr. Melenhorst is one of the first researchers to develop CAR T cells and participate in the therapy’s earliest clinical trials. He now leads the Cell Therapy and Immuno-engineering Program (CTIP) focused on improving CAR T-cell success rates and reducing costs.  

Under Dr. Melenhorst's mentorship, Dr. Arunachalam is learning how to carry out translational studies on CAR T-cell trials and plans to bring that expertise back to his hospital. His research, recognized by ASH, identifies biomarkers that predict whether CAR T-cell therapy will work, based on blood samples from patients in a multicenter clinical trial. 

“Better prediction methods will help make sure everyone who gets CAR T-cell therapy has the best chances for success while reducing wasted resources and sparing patients unlikely to respond,” he says. “I’ve built strong connections here and look forward to continuing these collaborations when I return to India.” 

Dr. Coutinho de Oliveira’s ASH-recognized research project used patient-informed genetic screening to find genes that help CAR T cells persist longer in the body and maintain superior cancer-fighting potency. CAR T cells need to be capable of replicating in our bodies just like cells that were not genetically engineered. If CAR T cells remain in the body, the health center does not need to spend resources engineering new cells and the patient doesn’t need to spend time and energy getting new infusions. 

Before Dr. Coutinho de Oliveira joined Dr. Melenhorst’s lab, she worked on vaccines against parasitic infections. 

“Regardless of whether I am looking at vaccines or CAR T-cell therapy, I am using the same tools and (more importantly) the same mindset to study the immune system,” she says. “It’s all about applying those tools and that mindset creatively.” 

The researchers also presented a poster on how the cancer drug Venetoclax enhances CAR T cells’ activity in chronic lymphocytic leukemia (CLL). CAR T-cell therapy has shown remarkable success in several blood cancers, but achieving similar outcomes in chronic lymphocytic leukemia (CLL) has been significantly more challenging. The Melenhorst lab previously showed that T cells in CLL were less functional and fewer in number, which limited how well they could be engineered into CAR T-cell products. Venetoclax seems to overcome these problems. 

The project is the basis for a Blood Cancer United (formerly Leukemia and Lymphoma Society)-funded clinical trial that the Melenhorst Lab has launched with Cleveland Clinic oncologist Paolo Caimi, MD. 

Drs. Arunachalam and Coutinho de Oliveira were both supported by seed funding from VeloSano, Cleveland Clinic's cancer research fundraising movement. VeloSano supports groundbreaking research by directing funds to the highest priorities—accelerating the delivery of lifesaving treatments to patients as swiftly as possible. Both researchers also credit Dr. Melenhorst’s guidance for shaping their approach to science. 

 “Dr. Melenhorst helped us be more critical about our own work so we never stop learning,” says Dr. Coutinho de Oliveira.  

Both researchers also received Travel Awards from the Cleveland Clinic Research Education & Training Center to present their research projects at the conference. After their presentations, the team took on a different kind of challenge: the ASH annual 5K run.  

“I told Beatriz I would only run if Arun joined as well. She got him to agree by telling him, our boss wants you to do this race,” Dr. Melenhorst laughs. “We’ve been joking that this proves collaboration extends outside the lab.”