University of Maryland Greenebaum Comprehensive Cancer Center Offers Novel Next-Generation CAR T-cell Therapy for B-cell Lymphomas in First-in-Human Clinical Trial

November 25, 2024

Researchers at the University of Maryland Greenebaum Comprehensive Cancer Center (UMGCCC) are conducting a first-in-human clinical trial of a novel next-generation CAR T-cell therapy to treat patients with recurrent or difficult-to-treat B-cell lymphomas, which are cancers of the lymphatic system.

The treatment, which is comprised of cancer patients’ own genetically engineered T-cells, or immune cells, is called “tri-specific” chimeric antigen receptor (CAR) T-cell therapy because it targets three antigens, or proteins, on the surface of the cancer cells. The goal is to boost the immune system’s ability to recognize the cancer, destroy it and prevent recurrence.

“We have four approved CAR T-cell therapies for B-cell lymphoma, but too many patients relapse, almost half within the first two years,” said Djordje Atanackovic, MD, Professor of Medicine at the University of Maryland School of Medicine (UMSOM) and the study’s principal investigator. “There is an urgent medical need to improve the treatment’s success rate.”

About 82,000 people in the U.S. are diagnosed every year with B-cell lymphomas, which develop in white blood cells in the lymphatic system. Most are non-Hodgkin lymphomas and can be aggressive or slow growing.

Dr. Atanackovic said that the Phase I trial funded by a grant of nearly $1 million from the Maryland Stem Cell Research Fund (MSCRF) will determine the safety and efficacy of the treatment, which has shown promise in pre-clinical models. It could provide “proof of principle” for this novel approach, which, he said, could potentially also be used to treat other cancers, including solid tumors.

UMGCCC is the only cancer center in the Maryland, Delaware, Virginia and Washington, DC region to offer this type of CAR T-cell treatment. One of only 57 National Cancer Institute (NCI)-designated comprehensive cancer centers in the U.S., UMGCCC is located within the University of Maryland Medical Center (UMMC) in Baltimore, the academic flagship hospital of the University of Maryland Medical System (UMMS).

Researchers plan to enroll up to 15 patients with B-cell lymphoma who have relapsed or refractory (difficult-to-treat) disease after receiving one or more treatments, which could include chemotherapy, other drug therapies, a stem cell transplant or previous CAR T-cell therapy.

The CAR T-cell therapies approved by the U.S. Food and Drug Administration (FDA) to treat patients with B-cell lymphoma and other blood cancers target only one antigen, CD19, on the cancer cell’s surface. This new treatment targets CD19 and adds two other antigens, CD20 and CD22, along with additional molecules to help stimulate T-cell expansion and survival.

“We need to do more. One target is not enough,” said Dr. Atanackovic, the Director of Cellular and Vaccine Immunotherapy at UMGCCC and Medical Director of its Fannie Angelos Cellular Therapeutics GMP Laboratory. He explained that when B-cell lymphomas recur they often lose the CD19 target. “This is a very well-known tumor escape mechanism,” he said. “If we target three different antigens at the same time, it will hopefully make it much more difficult for tumor cells to escape detection.”

For the first time, UMGCCC patients enrolled in this trial will be treated with a cellular immunotherapy produced in-house in the cancer center’s cell-processing laboratory instead of awaiting cell production and availability from a pharmaceutical company.

“One advantage of producing the cells in our own facility is that they can be available much earlier,” Dr. Atanackovic said. “We are able to produce billions of clinical-grade cells and have brought production time down from 14 days to eight days.”

The laboratory, which is led by Dr. Atanackovic and Kim G. Hankey, PhD, an Associate Professor of Radiation Oncology at UMSOM, was built and equipped with the support of donors such as the late Peter Angelos, the former owner of the Baltimore Orioles, and Neil Kishter, a financial services executive.

Dr. Atanackovic and his team have been working with Miltenyi Biotec, a Gaithersburg, Md., biomedical research company, to develop a first-in-human clinical trial to evaluate this unique CD19.20.22 CAR T-cell therapy in patients. The treatment, which was first developed by a Miltenyi-owned company, not only targets three antigens on the cancer cell’s surface but also contains two proteins, ICOS (inducible T-cell co-stimulator) and OX40, to help boost T-cell activation and survival.

UMGCCC is a regional leader in providing CAR-T cell therapy for blood cancers. It was the first center in the Maryland, Virginia, Delaware and Washington, DC region and among the first in the U.S. to be certified to treat patients with CAR T-cell therapy for lymphoma, multiple myeloma and leukemia. The center’s Transplant and Cellular Therapy (TCT) Program has treated nearly 500 patients with engineered T-cells to date, according to Aaron P. Rapoport, MD, the program’s Director and the Gary Jobson Professor in Medical Oncology at UMSOM.

“In addition to offering FDA-approved therapies to patients, we have a very robust clinical research program, with our investigators leading studies like this tri-specific clinical trial to help make cell-based immunotherapies more effective and potentially available for more patients,” Dr. Rapoport said, adding, “Having our own on-site cell-processing laboratory with state-of-the-art equipment enables us to be at the forefront of cell-based immunotherapy research.”

“After months of preparation, we are very excited to open this clinical trial for B-cell lymphoma patients whose cancer has recurred or not responded to previous treatments,” Taofeek K. Owonikoko, MD, PhD, UMGCCC’s Executive Director and the Marlene and Stewart Greenebaum Distinguished Professor of Oncology at UMSOM, said. “As an NCI-designated comprehensive cancer center, we are committed to advancing new therapies and bringing promising scientific discoveries into the clinic for the benefit of cancer patients in Maryland, the region and beyond.”

Mark T. Gladwin, MD, the John Z. and Akiko K. Bowers Distinguished Professor and Dean of UMSOM, and Vice President for Medical Affairs at University of Maryland, Baltimore, said, “CAR T-cell therapies continue to evolve to stave off recurrence of cancer, and an early study shows promise in targeting more than one antigen on the surface of cancer cells. This new trial, which our Greenebaum Comprehensive Cancer Center is uniquely qualified to conduct, should reveal crucial information on how these therapies keep the immune response boosted and ultimately improve the duration of the immune response.”