Enhanced CAR T-cell therapy may improve treatment options for patients with B-cell blood cancers

Results from a phase I clinical trial led by The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) show a possible way to improve therapy options for patients with relapsed or treatment-resistant B-cell blood cancers.

The findings were published in Blood Cancer Discovery.

Researchers were able to build on earlier work done at Ohio State that used CAR T-cell therapy to enhance treatment of B-cell blood cancers. About half of all blood cancers are B-cell blood cancers, including lymphoma and some leukemias.

This trial tested CAR T-cell therapy targeting three proteins-CD19, CD20 and CD22-and used a different protein called OX40 to boost immune response in patients.

This was the first time a CAR T-cell clinical trial used OX-40 to enhance the process and improve tumor death. Results from our trial could lead to better therapeutic outcomes for patients who may have limited options after their B-cell blood cancer has returned or their therapy stopped working."

Sumithira Vasu, MD, professor of hematology and member of the Leukemia and Hematologic Malignancies (LHM) Program, study's first and corresponding author, OSUCCC – James

The team also used a faster process to collect, prepare and return the cells to the patient in just six days. This resulted in positive outcomes with minimal side effects for the patients.

"It has been suggested that fresh cell infusions are preferable, and we were able to show feasibility of rapid manufacturing time and infusion of the fresh cells," said lead senior co-author Lapo Alinari, MD, PhD, associate professor of hematology and member of the LHM Program at Ohio State. "This resulted in meaningful clinical activity with minimal side effects in B-cell non-Hodgkin lymphoma, and remission in mantle cell lymphoma, follicular lymphoma and diffuse large B-cell lymphoma."

How does CAR T-cell therapy work?

CAR T-cell therapy removes cancer-fighting T cells from the patient's immune system, modifies those cells in a lab to strengthen their ability to kill cancer cells, and returns the cells to the patient via an infusion.

The cell therapy typically targets the CD19 protein that plays a large role in B-cell blood cancers. In previous animal studies, scientists at other institutions developed a CAR-T-cell therapy that also targeted two additional proteins-CD20 and CD22-and it showed increased effectiveness.

"Even though CAR T-cell therapy has revolutionized therapy for patients with B-cell blood cancers with high rates of remission, many patients will relapse after CAR T-cell therapy, and often within the first year," said Vasu. "Patients are then left with limited treatment options."

Eighteen patients with a median age of 64 were enrolled in the clinical trial, and 16 were treated with the OX-40 protein to enhance the CAR T-cell process. All enrolled patients had previously received a median of three types of therapy before receiving the enhanced cell therapy.

"While our trial showed encouraging outcomes for patients with B-cell non-Hodgkin lymphoma who were treated with our enhanced CAR T-cells, more research in larger patient groups is needed," said senior co-author Marcos de Lima, MD, professor of hematology at Ohio State.