Microbubble cell separation can make next generation treatments, such as CAR T-cell therapy, more accessible.
The human body can defend itself against a multitude of infectious diseases and harmful pathogens, but it has its limitations. The body struggles, for example, to successfully identify and destroy cancer cells.
Our immune system has all the requisite defenses, such as T cells, which are a type of lymphocyte that find and destroy defective cells. However, it can be difficult for T cells to differentiate between a normal healthy cell and a damaging cancerous cell. Therefore, cancer cells can go undetected, multiplying rapidly within the body.
Scientific breakthroughs are finally enabling T cells to target cancerous cells. Chimeric antigen receptor (CAR) T-cell therapy, a type of adoptive cell transfer, is a branch of immunotherapy whereby T-cells are collected, genetically altered, and fed back into the bloodstream. These genetically modified CAR T-cells are designed to recognize and target a specific antigen on the enemy cancer cells, priming T cells to attack and kill cancer cells.
There have been significant advancements in CAR T-cell therapy in treating blood cancers, such asleukemia and lymphoma. A recent study published in Blood Advances suggests that CAR T-cell therapy has improved long-term quality of life, with 76% of patients also achieving remission.1
The benefits of this treatment are clear, yet it remains unattainable for a large portion of the population who cannot afford to pay for it. The most efficacious cell therapy treatments remain prohibitively expensive for patients, including CAR T-cell therapy, which can cost more than $500,000 for a single treatment. This is often because the current workflows and manufacturing practices required for the creation of cell therapies are expensive and labor intensive.2
By 2040, there will be 28 million more cancer cases each year globally. Thus, scientists need to work to make the best treatments affordable for all cancer patients. By improving the way scientists separate cells, professionals can make cell therapies even more effective and less expensive, which improve accessability for all patients.3
All CAR T-cell therapy methods have one thing in common: the need for T-cell isolation. Therefore, optimizing this process will have dramatic effects on the overall process of cell therapy, cutting costs and improving efficacy.
Although current methods on the market have a multitude of limitations, they have been utilized for many years as innovation in the industry has grounded to a halt. For example, fluorescence-activated cell sorting (FACS) is a type of flow cytometry that uses fluorescent markers to target and isolate cell groups, and it is now the current standard in many clinical and research labs. Although a highly versatile technique, its processes are slow, expensive, and complex, with a low cell recovery rate average between 50% and 70%.
Magnetic-activated cell sorting (MACS), on the other hand, uses magnets to isolate targeted cells from the rest of a biological sample. As one of the most common cell separation technologies used today, this method is similarly highly versatile; however, MACS can also lead to significant hidden costs due to the expensive equipment. On top of this, its inability to facilitate multiple samples at the same time and its harmful environmental effects makes the method far from ideal.
In terms of collection for cell therapies more specifically, MACS as a method of separation does not scale well, making the vast amount of cells needed for CAR T-cell therapy difficult to attain. Furthermore, the tendency for this method to exhaust collected cells due to its harsh nature makes it a very poor cell separation technique for cell therapy treatments. The process of genetically modifying cells to target cancer already exhausts cells. Therefore, if they go into this process already damaged from MACS, they are less likely to survive and ultimately deliver an effective treatment to the patient.
The current methods on the market for extracting T-cells from a leukopak are holding back progress for cancer treatments. The current time-consuming and laborious methods require complex and specific devices that take a lot of effort to operate and are hard to store. Being both expensive and complex, they are difficult to scale and slow crucial treatment time.
This is where microbubbles provide an answer, offering a completely new paradigm shift in a market that has remained unchanged for more than 30 years. Microbubbles are air-filled, thin, silica-shelled hollow particles that can be used to easily and efficiently target and then separate specific cells within a sample.
Using negative selection, microbubbles specifically target and bind to all of the cells within the sample except T cells, at which point, their buoyancy allows them to float to the top. Self-isolating using gravity alone, the microbubbles can then be easily removed, along with their bound cells, from the top of the sample. Thus, leaving the T cells completely untouched at the bottom of the vessel and ready for downstream use.
Microbubbles are an efficient and cost-effective way to isolate cell populations. As the whole process is contained within a single vessel, this method allows for a dramatically simplified workflowand requires significantly less manpower to process a large amount of cells.
The process takes 60 minutes from start to finish, saving precious time between cancer diagnosis and treatment. This can also be completed on a mass scale, with the ability to run multiple samples at the same time.
The industry must strive to ensure that the efficacy of CAR T-cell therapy is maximized to improve care and recovery for all individuals living with malignancies. In the manufacturing process, if the cell sample is isolated with microbubbles, it will not undergo any harsh magnetic forces that can damage and exhaust the cells. This ultimately makes them less effective at killing cancer cells once reinserted into the patient’s bloodstream. Instead, this cell separation approach is gentle, minimizing shear forces to preserve the quality and viability of the T-cells.
By producing a higher purity and yield of cells, microbubble cell separation techniques not only improve the efficiency of cell therapy for cancer but also makes the treatment more cost effective for both patient and supplier.
Cell therapies are currently the best hope for patients with cancer and represent the most exciting, cutting edge sciences in oncology. Now, manufacturing and workflow practices need to catch up to be able to provide these treatments to everyone, not just the wealthy.
Microbubble technology isolates T cells quickly and effectively at a relatively low cost compared to traditional methods. Thus, CAR T-cell therapy, as well as a whole array of other cell therapies, have the potential to be transformed into more potent and economical treatments.
Microbubbles provide a long-awaited solution to the whole pharmaceutical and bioprocessing industry, which needs to shift from outdated methods of separation to a more affordable and overall successful method.
About the Author: Brandon McNaughton, PhD, is the chief executive officer and co-founder of Akadeum.