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Using Gravity To Separate T Cells Could Speed Up Cancer Treatment

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While surgery, chemotherapy and radiotherapy are commonly used in cancer treatment, researchers are increasingly looking to alternative treatments such as CAR T-cell therapy, which leverages the human immune system to target and destroy cancer cells.

For CAR T-cell therapy to be utilized, T cells must be isolated from the patient or a suitable donor and modified ex vivo, before being administered to the patient. Traditional methods of cell sorting come with several challenges, for example, they can be expensive, time consuming, and in some instances, may even cause damage to the cells. Microbubbles, on the other hand, can separate the target cells without causing any harm and are simpler to use than other methods.

Technology Networks spoke to Dr. Brandon McNaughton, CEO and co-founder of Akadeum to find out more about this technology, its applications and how it could improve cancer treatment.

Kate Robinson (KR): How is cell separation relevant to cancer treatment?

Brandon McNaughton (BM): Autologous CAR T-cell therapy is a highly complex and innovative new therapy that utilizes the body’s own immune response to target cancerous cells. Although surgery, chemotherapy and radiotherapy are viable treatments that are often recommended as part of a cancer patient’s treatment plan, researchers are increasingly looking to leverage the human immune system as a new defense against cancer.

When the immune system helps the body fight infections and other diseases, white blood cells, specifically lymphocytes, are an essential part of this response. T cells are one type of lymphocyte that are primed to move around the body to find and destroy cancer cells. Although T cells are good at fighting against threats, they can struggle to differentiate healthy cells from cancerous cells. This leads to cancer cells going unchecked and multiplying rapidly within the body.

However, scientists now have the ability to isolate, genetically modify and reintroduce T cells into patients so that they can effectively recognize and destroy cancer cells. This means that these cells can be reprogrammed to produce proteins on their surface called chimeric antigen receptors, or CARs. The CARs recognize and bind to specific proteins, or antigens, on the surface of cancer cells. It is through this mechanism that the immune system is now primed to recognize and destroy cancerous cells.

For this treatment to be a success, T cells must first be isolated from the rest of the leukopak (a sterile bag of apheresis product enriched with white blood cells), which also contains plasma, platelets and red blood cells. It is this isolation process that can be revolutionized, making CAR T-cell therapy potentially more effective and also increasing accessibility through reduced cost. Currently, this type of therapy has long wait times and can cost upwards of $500,000 per course of treatment.

KR: What are microbubbles, and how are they used for cell separation?

BM: Microbubbles are microscopic floating particles that have a silica shell and an air core. Microbubbles are used to target a wide range of analytes, including cells, nucleic acids, proteins, exosomes and more from a variety of complex biological samples ranging from blood to wastewater.

There are two main types of separation performed when using microbubbles: positive and negative selection. In positive cell selection, all desired cells are separated to the top of the solution alongside the microbubble. In negative selection, all unwanted cells are floated to the top of the sample, leaving target cells untouched at the bottom of the container. The choice of positive or negative selection ultimately depends on the desired downstream use.

When isolating T cells in cell therapy workflows, negative selection can be a desirable approach because it leaves T cells untouched and in pristine condition. For this workflow, the microbubbles are mixed with a leukopak sample. The microbubbles then bind to everything except the desired T cells. After the microbubbles attach, the natural buoyancy then allows them to float to the top of the sample container, bringing their bound targets to the top of the sample. The desired T cells remain at the bottom of the sample ready for removal. The power of this method is that it is self-separating within a single container, representing a massive simplification and improvement over other methods. 

KR: How does microbubble cell separation differ from other methods of separation?

BM: Two common cell separation techniques used within the industry at the moment are fluorescence-activated cell sorting (FACS) and magnetic-activated cell separation (MACS). FACS uses fluorescent markers to identify specific cell types and then sorts them. This process takes a significant amount of time as the cells have to be arranged in a single file line to identify and sort different cell types. MACS uses magnetic particles attached to specific cell types and a magnet to physically separate the cells. MACS is limited in scalability and gentleness due to the magnet. Both methods have been around for 30 years or more and do not meet all of the rapidly emerging needs of next-generation technologies in diagnostics and cell therapy.

In comparison, buoyancy-activated cell sorting (BACS) was designed and developed to meet the increasing demands found in the life sciences. BACS works by using flotation to separate cells: microbubbles capture target cells and quickly float them to the surface of a biological sample for removal, maintaining the quality and viability of sorted cells. Not only is the process gentle on cells, but the workflow for the process is also greatly simplified. The process is fast, efficient, gentle and scalable.

KR: Are there any benefits of this technology over fluorescence-activated or magnetic-activated cell sorting?

BM: Because flotation needs very low forces to work, using BACS with microbubbles is the most gentle way to isolate cells, and due to its simplicity, it is one of the fastest, most efficient and scalable methods with some protocols being as low as 10 minutes. The high purity and yield rates with BACS, in combination with workflow advantages, makes the process highly reliable, robust and cost effective. These are just a few of the reasons users around the world have incorporated microbubbles into their workflows.

KR: Is there anything else you would like to highlight about this technology?

BM: Cell and gene therapy manufacturing tools are just the beginning for Akadeum. There are multiple markets and industries that we believe will reap the benefits of the microbubble. For example, microbubbles can be used to detect dangerous viruses in wastewater, helping to accurately monitor outbreaks and potentially reduce the spread of disease in the next pandemic. We see no end in sight to the potential of this technology. We are early in the process and the applications seem limitless. At Akadeum, our goal is to fully develop and utilize this powerful platform. Our hope is to not only transform outcomes and access for cancer patients, but deploy this technology broadly for society as a whole.

About the interviewee:

Brandon McNaughton is the CEO and Co-Founder of Akadeum

Dr. Brandon McNaughton was speaking to Kate Robinson, Assistant Editor for Technology Networks.