Innovative technology simplifies T cell harvesting for cancer immunotherapy

CAR T cell immunotherapy, which uses a patient's own modified immune cells to find and destroy cancer cells, can produce dramatic results when treating blood cancers like lymphoma and leukemia and shows promise against solid tumors.

But harvesting T cells, a type of white blood cell that helps the immune system fight germs and protect against disease, is difficult and expensive-limiting the use of this potentially life-saving therapy to major cancer centers and after other treatments have failed.

Now a team of researchers at Case Western Reserve University is developing a new device to harvest T cells that might make CAR T cell therapy less expensive and more widely available. The device, called CAPGLO (for capture and glow), uses a magnetic field to "capture" T cells and visualize them with fluorescent tags that make them "glow."

The laboratories of Robert Brown, a physicist in the university's College of Arts and Sciences, Susann Brady-Kalnay, a cell biologist, and David Wald, an immunologist at the School of Medicine, reached across disciplines and schools to collaborate on this technological innovation.

I hope that we could bring the cost of immunotherapy down so it could be first-line therapy rather than end-stage treatment. For some people, this is a curative therapy. For others it offers significant survival benefits. We need to make it more accessible to everyone."

Brady-Kalnay, the Sally S. Morley Designated Professor of Brain Tumor Research and a member of the Case Comprehensive Cancer Center (Case CCC)

CAPGLO is expected to be very inexpensive to manufacture. "If we can really do it, for a few hundred dollars rather than thousands or hundreds of thousands, that's where this treatment reaches equity," said Brown, a Distinguished University Professor and Institute Professor of physics.

As co-leader of the Immune Oncology Program, Wald directs the Case CCC clinical Cell Therapy Lab that manufactures CAR T cell therapies for patients. He has developed an ultra-fast procedure to establish and expand CAR T cells in less than 24 hours.

Conventionally harvesting T cells

T cells are extracted from a cancer patient's blood using "leukapheresis," where blood is removed and centrifuged to harvest immune cells and then returned to the patient. This requires specialized equipment, costing hundreds of thousands of dollars, as well as removing and replacing a large volume of blood. 

The cells are then transformed into cancer killers in the lab by adding a protein called a chimeric antigen receptor, or CAR. These cells-now called CAR T cells-are multiplied in the lab and reinfused into the patient's bloodstream within a few days to weeks. The CAR protein acts like a navigation system to help track down and kill cancer cells. For some patients with even very advanced cancers, CAR T cell therapy can eradicate their disease.

CAPGLO wouldn't require more than about a half-pint of a patient's blood-the amount typically needed when donating blood.

This isn't Brown's first foray into the physics of blood. He and Case Western Reserve senior research associate Robert Deissler developed a technique to diagnose malaria that relies on the fact that malaria-infected blood carries extra iron-as iron-containing crystals, which are magnetic. This simple diagnostic tool using magnets to detect malaria in blood samples earned them a Patent for Humanity in 2016 from the U.S. Patent and Trademark Office, an award recognizing innovators for game-changing technology that meets global humanitarian challenges.

Using magnets to isolate T cells

For this new project, the researchers make the T cells magnetic. Kathleen Molyneaux, a senior research associate in Brady-Kalnay's lab, coats tiny magnetic beads with a protein designed to snag T cells in a blood sample and bind them to the bead's surface.

Then, using CAPGLO and a magnetic field, Brown and Deissler can separate the magnetized T cells from the red blood cells and plasma, collecting the T cells in a small tube.

As a final step, the investigators plan to harmlessly snip off the beads, leaving a population of T cells ready for chimeric transduction in Wald's lab. The goal is to take and process a patient's blood within an hour, so the T cells don't become damaged.

The researchers received a grant from the CWRU Technology Validation and Startup Fund, a program supported by the Ohio Third Frontier, to explore the viability of the technology.