How the Integration of Microbubble Technology and Cell Separation Systems Provides a Breakthrough in Cancer Treatments

The emergence of chemotherapy in the 1950s heralded a groundbreaking new treatment for metastasized cancers. In the 21^st century, cell therapies are now promising to revolutionize the way we fight cancer, well on their way to becoming first-line targetable treatments for the disease. 

The President’s Budget for 2024 includes $1.7 billion for dedicated Cancer Moonshot activities across the Department of Health and Human Services (HHS), in addition to a total investment of $7.8 billion at the National Cancer Institute (NCI) to drive progress on ways to prevent, detect, and treat cancer. The Budget also provides an increase of $1 billion for the Advanced Research Projects Agency for Health (ARPA-H), for a total of $2.5 billion, to drive innovative health research and speed the implementation of breakthroughs that will/can transform the treatment, prevention, and early detection of cancer and other diseases. Therefore, continuous developments within the industry, bolstered by strong government funding, mean that new treatments are constantly improving the outcomes for patients globally.

By applying chemotherapy alongside other traditional methods such as surgery and radiotherapy, oncologist are able to achieve high rates of remission. However, chemotherapy is also associated with a long list of side effects, such as hair loss, nausea, headaches, and muscle damage, which can drastically reduce a patient’s quality of life.

Cell therapies have provided new highly personalized drugs which are also considerably more targeted in the way they kill cancer cells, and reducing detrimental side effects. One such treatment is Chimeric Antigen Receptor (CAR) T cell therapy (also known as adoptive cell transfer), a type of immunotherapy which has become a groundbreaking treatment for cancers such as leukemia and lymphoma.

Upcoming Cell Therapies: CAR T cell Therapy 

Immunotherapies work by strengthening the power of the patient’s own immune system to attack tumors. T cells, a type of white blood cell are an essential part of this immune response, attaching and killing foreign antigens. However, T cells often have issues detecting and destroying cancerous cells: this is where CAR T cell therapy can help. Autologous CAR T cell therapy, like other immunotherapies, aims to stimulate a host response that produces long-term tumor destruction, which has provided long-lasting remission and has even cured patients. 

T cells can be collected from the patient, genetically modified, and reintroduced back into the patients’ bloodstream. Once genetically modified, these T cells produce proteins on their surface called chimeric antigen receptors, or CARs. It is these CAR receptors that have the ability to specifically target cancer cells, recognizing and binding to the antigens present on the surface of the cancer cell. This treatment is completely customizable, using each patient’s own T cells meaning they are less likely to be rejected by the body. After being multiplied within the laboratory, these modified T cells are then infused back into the patient. At which point, the CAR T cells proliferate, now primed to recognize and eradicate unwanted cancer cells. 

In the last decade, several cell-based immunotherapeutic cancer treatments using CAR T cells have been approved by the FDA. These novel courses of oncological treatment have resulted in years of remission in some adult and pediatric leukemia patients. However, the therapy can cost upwards of $500,000, partly due to the fact that current procedures and technologies are labor-intensive and difficult to scale up in manufacturing processes. Customers are therefore forced to settle for mediocre treatment performance at an increased price due to dated technology.

The answer to providing more effective and affordable cancer treatments lies in making the T cell isolation process more streamlined. By using microbubble technology to gently separate T cells from a donor’s apheresis material, cell therapy manufacturers can isolate healthier cells for downstream use. 

Microbubbles: Cell Separation through Floatation 

As cancer treatments evolve, so too must cell separation and workflow methods. The current standard of cell separation methods used in the industry include Magnetic-activated Cell Sorting (MACS) and Florescence-activated Cell Sorting (FACS). While MACS utilizes magnetic particles to isolate target cells from solutions, FACS employs flow cytometry and fluorescent probes to sort and separate cells. However, both methods are harsh on cells, resulting in slower, expensive, and ultimately subpar workflows. 

Buoyancy Activated Cell Sorting (BACS) utilizing microbubble technology provides a cheaper, simpler, and more effective alternative. These miniature, gas-filled microbubbles bind either target or unwanted cells to facilitate negative selection, positive selection and depletion manufacturing workflows. . Their natural buoyancy allows them to rise to the top of the solution, where they can be removed or recovered for downstream use. 

Microbubble protocols take less than 60 minutes from start to finish and are highly scalable, allowing for multiple sample processes to take place simultaneously. This ultimately reduces the time patients must wait between sample collections to treatment administration. Furthermore, as microbubbles only require gravity to separate themselves along with their target cells, this exceptionally gentle workflow preserves the quality and viability of target cells, ensuring their quality for effective downstream use.

Microbubble Cell Separation Instrument 

The microbubbles’ seamless workflow capabilities can be further perfected through the use of a closed, automated system. The Alerion™ buoyancy-based cell separation instrument is a system designed to separate T cells from apheresis material using microbubbles. This instrument promises to speed up the cell separation process, increase cell recovery rates, automate several manual steps, improve sample processing robustness, decrease user error incidence, and enhance cellular health. By automating microbubble separation manufacturing processes, lab technicians are able to reduce manual labor and avoid any human error, ultimately providing patients with better treatments at a better price for cancer patients. This is the new and modern method for breakthrough treatments such as immunotherapies like CAR T cell therapy. 

The Future of Cell Separation and Cancer Treatment 

For the first time, cell therapy manufacturers have a choice of the cell separation technology they use and microbubbles have revolutionized a market which has remained largely stagnated for decades. Coupled with cell separation instruments, such as the Alerion™ which achieves cell recovery rates of 90% and above, manufacturers can expect more healthy cells for use in cell and gene therapy workflows compared to other technologies. With a nearly infinite range of applications, microbubbles are revolutionizing a multitude of industries. By harnessing this technology to create more effective and affordable cell therapies, patients can expect a better quality of care and superior treatment outcomes.