COLUMBUS, Ohio – A five-year, $3.04 million grant from the National Cancer Institute (NCI) will help researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) study the effectiveness of a new triple-target cellular therapy they have developed to more effectively treat patients with relapsed or treatment-resistant B-cell malignancies. Sumithira Vasu, MD, Lapo Alinari, MD, PhD, and Marcos J. de Lima, MD, all of the Division of Hematology at Ohio State and members of the OSUCCC – James Leukemia Research Program, serve as principal investigators of this first-in-human, phase I and on-going clinical trial. It will test a form of chimeric antigen receptor T-cell (CAR T-cell) therapy that targets three proteins instead of just one in patients with relapsed or treatment-resistant B-cell non-Hodgkin lymphoma, B-cell acute lymphoblastic leukemia, B-cell prolymphocytic leukemia or chronic lymphocytic leukemia. “Despite high rates of complete remissions, many patients relapse after CAR T-cell infusion and often within the first year. Patients have limited treatment options, which highlights the need for novel CAR T-cell products,” said de Lima, who directs the Blood and Marrow Transplant and Cellular Therapy programs at the OSUCCC – James. Unlike commercially available CAR-T therapies, which are shipped to commercial labs for processing, this new CAR-T therapy is made in house at the OSUCCC-James cell therapy lab. In addition to offering a more targeted option, experts say this new CAR-T drug can also be manufactured and administered more quickly to patients in need. “By creating an in-house CAR T-cell therapy manufacturing program, we can increase timely access to the therapy. While the process is faster than it once was, it can still take precious weeks to get these super-charged cells back to treat the patients, who do not typically have that type of time to spare,” said Vasu. CAR T-cell therapy—which involves removing a patient’s T cells, modifying them in a laboratory to strengthen their ability to kill cancer cells, and returning them to the patient—has revolutionized cellular immunotherapy for patients with B-cell malignancies. Miltenyi Biotec provides the vector that allows the clinical team to manufacture CAR T-cells in the laboratory. “This is the first investigator-initiated trial at Ohio State in which the cell therapy was manufactured at the OSUCCC – James and has received NIH funding,” said Alinari. CAR T-cell therapy typically targets a protein called CD19 that plays a large role in B-cell malignancies; however, scientists at other institutions have developed a CAR T-cell therapy that simultaneously and effectively targets the CD19, CD20 and CD22 proteins in preclinical models of lymphoma. The OSUCCC – James scientists have validated these findings and will address limitations of commercial CD19 CAR Ts through an on-going clinical trial that tests the effectiveness of a CAR T-cell therapy they have manufactured in Ohio State’s cell therapy lab to target the CD19, CD20 and CD22 proteins. The trial will determine the feasibility and safety of their triple-target CAR T-cell therapy treatment and establish a recommended dose for a projected phase II study. It also will identify key mechanisms of efficacy and shed light on how these therapies work and sometimes fail. “By targeting three proteins at the same time (CD19, CD20 and CD22) in patients with B-cell malignancies, our goal is to improve on the results of single-antigen CAR T-cell therapies,” said de Lima. In addition to the grant from the NCI, this on-going trial is also supported by funds from the Pelotonia Idea Grant Program. Since Pelotonia’s inception, the effort has allowed the OSUCCC – James to fund hundreds of faculty-led pilot research projects across 11 colleges and Nationwide Children’s Hospital. Projects span laboratory research in cells and tissue to increase foundational knowledge about cancer development and progression to clinical trials that evaluate new treatment approaches in humans. To learn more about CAR T-cell therapy, hematology research and patient cancer care at the OSUCCC – James, visit cancer.osu.edu/hematology.                                                                                              ### Media Contact: Mary Ellen Fiorino, Wexner Medical Center Media Relations, Mary.Fiorino@osumc.edu