Researchers streamline method to produce CAR-T cells in just 24 hours

Researchers streamline method to produce CAR-T cells in just 24 hours

Researchers at University Hospitals (UH) Seidman Cancer Center and a biotech startup have developed an optimized method for producing CAR T cells for immunotherapy in just 24 hours - an improvement over the team's previous benchmark of eight days and commercial providers typically take three weeks. The team is one of the first in the country to test this manufacturing approach.

This revolutionary new development promises to accelerate the delivery of CAR-T therapy to those who need it most - an important concern for hematologists and oncologists and their patients. Additionally, researchers at the UH Seidman Cancer Center say the rapidly produced CAR-T cells appear to be more effective than cells produced using traditional methods.

Why speed is important:Some evidence suggests that 25 percent of cancer patients scheduled for CAR-T therapy experience disease progression before they can be treated, with many waiting well over three weeks for delivery of a commercial CAR-T product.

“Some patients simply don't have a lot of time, so streamlining this manufacturing process and potentially even producing a more effective product is very important and will ultimately benefit many people,” adds James Martin, MD, an oncologist at UH Seidman Cancer Center. is the principal investigator of an upcoming Phase 1 clinical trial testing the new CAR-T manufacturing technology.

This work by UH scientists is fundamental to the field of CAR T-cell therapy and to the development of such products in other diseases such as acute leukemia or, in the future, some solid tumors.”

Koen van Besien, MD, PhD, chief of hematology at the UH Seidman Cancer Center and director of the Wesley Center for Immunotherapy and the Don C. Dangler Chair in Stem Cell Research

What is CAR-T therapy?

CAR-T therapy is a mainstay of modern immunotherapy for certain types of cancer. The procedure allows doctors to identify markers on the surface of cancer cells, take a person's own normal T cells and reverse engineer them to specifically look for cells with those suspicious markers to destroy the cancer. These genetically engineered cells are known as chimeric antigen receptors, or CAR-T cells.

The new manufacturing process developed here expands the benefits of this breakthrough therapy even further, researchers say.

“The faster CAR-T product appears to be more potent and effective,” says David Wald, MD, PhD, associate director for basic research at the newly expanded Wesley Center for Immunotherapy at the UH Seidman Cancer Center and associate professor of pathology at Case Western Reserve University School of Medicine. "We need to do clinical trials to know for sure, but at least in animal testing, the rapid CAR-T product is more effective than cells made using traditional methods. There appear to be significant advantages, not only in being able to make the product more efficiently and at a significantly lower cost, but we hope it will be more effective in patients too."

Clinical trial should start soon

In November, the UH Seidman Cancer Center, in collaboration with Case Western Reserve University's Case Comprehensive Cancer Center and the Cleveland Clinic, will launch a Phase 1 clinical trial of the rapid-production CAR T-cell product. The study will test the safety of so-called UF-KURE19 cells in adult patients with relapsed or refractory non-Hodgkin lymphoma. However, if the study is successful, the research team hopes to expand testing of rapidly manufactured CAR-T products to patients with other types of cancer.

"People are also working on rapid conditioning regimens, so hopefully delivery of the product to patients can be further improved in the future, but just reducing it to four or five days should result in clear and immediate benefits for cancer patients," Dr. Wald says.

Making the technology accessible to others

In developing this new technology, says Dr. Forest, the research team is making a concerted effort to make the manufacturing process simple and inexpensive to make it accessible to hospitals worldwide without advanced equipment.

"We're ultimately looking at this as a therapy that can be manufactured outside of a specialized Good Manufacturing Practices (GMP) laboratory so that it's more accessible to most major hospitals around the world, particularly in places and other countries where they don't have much of this sophisticated expertise and facilities that are currently needed to produce CAR-T cells themselves. The goal is to create a very simple, one-day process that doesn't require a lot of complex equipment or expertise."

Effect for patients

Dr. Martin and Dr. van Besien are optimistic about the difference the new CAR T manufacturing process can make for their patients.

“Especially for patients with multiple recurrent aggressive diseases, it is sometimes difficult to find appropriate therapies that keep their disease in check,” says Dr. Martin. "While waiting for the CAR-T product, the more lines of treatment someone goes through, the less chemosensitive it really is. Taking someone to the hospital and then giving them a cell product within a few days is going to make a big and meaningful difference to their disease control."

“This will help our sick lymphoma patients who often do not have the time to wait for the lengthy manufacturing process to receive life-saving CAR-T therapy,” adds Dr. van Besien added.

Source:

University Hospitals Cleveland Medical Center

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