For many years, the foundations of cancer treatments have been firmly set in surgery, chemotherapy, and radiotherapy. While these methods continue to be crucial pillars of treatment, new research has begun to transform the treatment landscape for people living with cancer. Over the past decade, scientists have shifted their focus inward, turning toward the patient’s own immune system as a treatment alternative.

Immunotherapies: Breaking Down the Door to Better Cancer Treatments
Immunotherapies strengthen the power of a patient’s own immune system to attack tumors. These treatments have shown the ability to shrink, and even eradicate, tumors. One particular form of immunotherapy, CAR T-cell therapy, has sparked significant excitement among researchers by showcasing its ability to eradicate advanced leukemia and lymphoma types, in some cases keeping the cancer at bay for many years.

Autologous CAR T-cell therapy, a subset of immunotherapy, works by collecting, genetically modifying, and reintroducing T-cells back into the bloodstream. As their name implies, T cells – which help orchestrate the immune response – are the backbone of CAR T-cell therapy. Currently, available CAR T-cell therapies are customizable for each individual patient, using their own T-cells and modifying them 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.

After multiplying the modified T-cells in the laboratory, they are then infused back into the patient. The CAR T-cells will then continue to proliferate in the patient’s body, recognizing and killing cancer cells that harbor the target antigen on their surfaces.

Significant progress has been made in CAR T-cell therapy and several long-term studies on the efficacy of the treatment have proven promising. For example, one clinical trial demonstrated an almost 62% remission rate at five years in children and adults with relapsed B-Cell Acute Lymphoblastic Leukemia.[1] This has made a significant difference given that many of these patients “were virtually untreatable” before receiving CAR T-cell therapy.[2]

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Although CAR T-cell therapies provide a lifeline to patients, they remain financially out of reach for a substantial portion of the population. For instance, 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. [3] Customers are therefore forced to settle for mediocre performance from dated technology at an increased price.

The answer to this predicament lies in an unexpected place: the T-cell isolation process. By revolutionizing how we isolate T cells from solutions and dramatically reducing the time it takes to an hour or less, researchers and manufacturers can reduce costs and waiting times whilst significantly increasing the effectiveness of treatments for patients.

Successful Cell Isolation Hinges on Efficient Methods 
All CAR T-cell therapies require the isolation of T-cells. These cells are extracted from a leukopak, an enriched apheresis product collected via leukapheresis, comprising of white blood cells, plasma, platelets, and red blood cells. Consequently, optimizing this extraction process promises to have a profound impact on the entire cell therapy workflow, reducing costs and enhancing the efficacy of treatments.

Existing methods on the market have persisted due to a lack of innovation in the field, yet they are associated with numerous limitations. The most widely utilized cell separation method on the market is magnetic-activated cell sorting (MACS). This method employs magnets to separate target cells from the rest of a biological sample. Despite being widely adopted, MACS is often accompanied by concealed expenses due to the costly machinery required to run it. The process is also hindered by its inability to handle multiple samples simultaneously, coupled with its damaging environmental effects.

Moreover, MACS lacks efficient scalability for cell therapies, making it less than ideal for the large quantities of cells needed for CAR T-cell therapy. Additionally, its harsh nature can deplete collected cells and impair their function before they have even entered the body. As the genetic modification process already strains cells, starting with cells stressed by MACS may result in reduced treatment effectiveness. Therefore, this method is ultimately an unsuitable separation technique for cell therapy treatments.

Current methods of extracting T-cells from a leukopak hinder progress in cancer treatments. Buoyancy-based cell separation technology in the form of microbubbles, offers a breakthrough – providing a welcomed fundamental shift in a field that has remained largely unchanged for more than three decades.

Microbubble Technology: Unlocking the Full Potential of Cell Separation
Microbubbles are air-filled, thin silica-shelled hollow particles that facilitate precise targeting and separation of specific cells within a sample. By employing negative selection, microbubbles attach to all cells in a sample except T-cells. Their buoyancy allows them to rise to the surface, leveraging gravity alone. The microbubbles can then be effortlessly removed, along with their bound cells, from the sample’s top. This process leaves T-cells untouched at the bottom of the vessel, ready for downstream use.

This buoyancy-based approach offers an elegant workflow for floatation-based separation, completing the entire procedure in just 60 minutes from start to finish. This preserves critical time between receiving the sample and treatment. Furthermore, the process can be scaled up to handle multiple samples simultaneously, producing exceptional yield.

The gentle nature of microbubble technology also avoids the harsh magnetic forces imposed on valuable target cells by MACS, which can damage and weaken cells. Using gravity alone to isolate cells therefore ensures their purity when reintroduced into the patient’s bloodstream. This approach minimizes any shear forces to preserve T cell quality and viability, ultimately producing more effective treatments for patients.

Microbubble technology maximizes both cell purity and yield, not only enhancing the potency of cancer cell therapies but also making treatment more cost-effective for both patients and providers.

Crossing the Threshold: Out with the Old and in with the New
The healthcare industry must strive to make the most of the effectiveness of CAR T-cell therapy, enhancing care and recovery for individuals battling all malignancies.

Cell therapies represent the most promising frontier for cancer patients, presenting cutting-edge solutions to a daunting challenge. The next imperative is for manufacturing and workflow practices to catch up, ensuring these treatments are financially viable to everyone in need.

Microbubble technology addresses the challenges posed by alternative cell separation techniques. It offers a paradigm shift in the field of cell separation, activation, and expansion, promising higher performance and lower costs to improve accessibility. This technology stands as a long-awaited solution for the pharmaceutical and bioprocessing industry, driving the transition from outdated separation methods to a more affordable and ultimately successful approach.

Reference
[1] Shah NN, Lee DW, Yates B, Yuan CM, Shalabi H, Martin S, Wolters PL, Steinberg SM, Baker EH, Delbrook CP, Stetler-Stevenson M, Fry TJ, Stroncek DF, Mackall CL. Long-Term Follow-Up of CD19-CAR T-Cell Therapy in Children and Young Adults With B-ALL. J Clin Oncol. 2021 May 20;39(15):1650-1659. doi: 10.1200/JCO.20.02262. Epub 2021 Mar 25. PMID: 33764809; PMCID: PMC8274806.
[2] Chimeric Antigen Receptor (CAR) T cell therapy: A remarkable breakthrough in cancer treatment. HEALTH AUGUST 21, 2023 [Article]
[3] Robinson KM Navigating the Financial Aspects of CAR T-Cell Therapy. WebMD, January 24, 2023.

Featured image courtesy © 2016 – 2023 Fotolia/Adobe. Used with permission.


DOI: https://doi.org/10.14229/onco.2023.11.23.001

Brandon H. McNaughton, Ph.D.1
Microbubbles: The Unlikely Key to Providing Accessible and Effective Cancer Treatments – Onco’Zine, November 23, 2023.
DOI: 10.14229/onco.2023.11.23.001
1 Akadeum Life Sciences

 

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