Doors could soon open wider for cell-based therapies, thanks to research underway in the University of Houston lab of Dr. Sergey Shevkoplyas, associate professor of biomedical engineering.
With funding from a Cancer Prevention & Research Institute of Texas grant, Shevkoplyas and his research team are seeking to revolutionize the first step in a patient’s individualized cell-based treatment: the harvesting of T-cells from the patient’s blood.
Shevkoplyas envisions a new device – simpler and more accessible than existing technology – that can serve many patients who cannot be reached today.
“No one has done this before, but I’m optimistic,” Shevkoplyas said.
Over recent years, cell-based therapies have grabbed headlines for their potential to convince a body’s natural immune system to launch a search-and-destroy mission against some types of disease agents. Cancer is the usual target, including some kinds of stubborn tumors that tend to defy traditional chemotherapy and radiation treatments. A few non-cancer applications, including Crohn’s disease and other autoimmune disorders, can also be treated with cell-based therapies.
Although the science is still in its early stages, positive reports inspire the general public to regard cellular therapies as almost a miracle. The development is indeed a landmark in medical history, but it’s not an instant or certain cure.
The trouble with T’s
Challenges begin with the very first step, which is collecting T-cells from a patient’s blood. T-cells, a critical part of a healthy immune system, travel through the bloodstream ready to attack invaders or bad cells that might threaten the health of the body.
In some cases, though, the T-cells don’t know how to recognize the target. That is where the art and science of cellular therapies steps in.
For many of those situations, T-cells can be custom altered so they can attach to a very specific part of a defective cell, then they can do their job of destroying the pathogen. Once altered, they are known as CAR T-cells (for chimeric antigen receptor-modified T-cells).
But first, they must be collected from the patient, or sometimes a donor.
The current method of T-cell collection, called leukapheresis, involves passing a large volume of patient’s blood continuously through a special machine, which separates T-cells via centrifugation and returns the rest of the blood back to the patient. The system does the job but is slow, taking several hours to complete a collection. The leukapheresis process itself damages many of the cells it captures, so the amount of processed blood must be large enough to accommodate the loss.
The leukapheresis machines are expensive to buy and run. They are also bulky and require specially trained technicians to operate. Add up these factors, and it’s hard to find one at work outside major medical centers in large cities of well-developed countries.
“If you have a brilliant system that is available to only a few, the impact is small,” Shevkoplyas said. “We looked at this and we said: ‘There’s got to be a better way’.”
A different idea
The research team envisions replacing the large centrifugation-based machines with a small device, about the size and shape of a small Frisbee, engraved with about a hundred tiny channels specially designed to separate T-cells from the rest of the blood cell by size, in a process called ‘controlled incremental filtration’ (CIF).
The device will be disposable and easy to operate, without a need for any complex equipment. Instead of attaching a patient to a leukapheresis machine and spinning the blood in a centrifuge to separate the T-cells, a technician would simply pass the blood through the device.
“The patient can come to a regional hospital for this procedure without any need to travel to a major hospital,” Shevkoplyas said. He also sees the devices being transportable enough to be taken almost anywhere, even to remote areas of the world.
“We want to democratize this process,” Shevkoplyas said.
In addition to being less expensive to build and operate, Shevkoplyas sees the new device as doing a better job, too. “It would extract the T-cells very efficiently with no damage to the cells.”
Because of this, the device will be able to collect sufficient number of T-cells from about a cup or two of whole blood obtained via a regular blood-draw, which is more gentle and much faster than leukapheresis, especially important for patients suffering with serious disease.
The team’s work is in its beginning stages, but already is showing good results.
“I see good progress. We’re ahead of the time frame,” he said.
The Cancer Prevention & Research Institute of Texas grant covers $200,000 of research expenses. The project, titled “Novel High-Throughput Microfluidic Device for Isolating T-cells Directly from Whole Blood to Simplify Manufacturing of Cellular Therapies,” is expected to continue through August 2021.