Tailored immune cell production scaled up

Prof. Lachmann uses various scalable systems to continuously produce specific mature human immune cells or to do so using induced pluripotent stem cells. Human immune cells and immune cell preparations play an increasingly prominent role in modern medicine, for example in new cancer treatments and in the development and testing of new drugs. To obtain these cells for health research, the industry has long relied on human donors or used cell lines from various cancers.

However, since every person and every cancer cell is unique, it was not possible to standardize the processes involved. This proved to be a major problem until two stem cell researchers from Japan and the UK made a major breakthrough in 2006. They then succeeded in transforming adult skin cells into induced pluripotent stem cells (iPSCs), which can then be transformed into different cell types. In recognition of this, Shinya Yamanaka and John B. Gurdon were awarded the 2012 Nobel Prize in Physiology or Medicine.

From small to industrial applications

Enter Prof. Nico Lachmann and his team from the Fraunhofer Institute for Toxicology and Experimental Medicine ITEM and Hannover Medical School (MHH) are now exploiting the ability of these iPSCs to divide and differentiate indefinitely. The researchers have developed an unprecedented method to continuously produce specific, mature immune cells from these iPSCs in scalable systems – from small to industrial applications.

This is done in an apparatus that looks like a large snow globe, where the stem cells are immersed in a solution and then kept in constant motion. Using new bioprocesses, they continuously spread the targeted immune cells. In addition, the iPSCs only need to be replaced after approximately three months to maintain consistent quality.

Immune cells on a large scale

The ingenious design – in 3D, rather than the previous 2D design on the bottom of a petri dish – is what really sets the process apart. This means that the researchers can produce significantly larger quantities of the designer immune cells and scale up as needed.

As Prof. Lachmann says: “We spent three years researching the ideal medium, angle and speed for the standardized production of immune cells from iPSCs, repeatedly adjusting many parameters along the way. This optimized method is a great asset to to research and evaluate drug candidates, as we can test their efficacy and safety directly in human target structures without resorting to animal testing, which actually goes a long way.”

Human immune response

Initially, his team specialized in macrophages, scavenger cells that fight bacteria and are an important element of the human immune response. The next step is for Prof. Lachmann and his team to set up cell-based potency tests. For example, for the benefit of medicine against cancer. These test systems can measure the potency of biological and bioengineered drugs and play an essential role in the quality control and release of active ingredients and drugs.

Based on their key technology for continuous production of macrophages, the researchers also plan to develop new production processes for several fully standardized immune cell products and cell-based immunotherapies, opening up many additional applications.

Application designer immune cells

The potential for designer immune cells is enormous. For example, they can be genetically modified to light up when they detect impurities in medicine. This has been very difficult to identify until now. Artificial skin tissue, already used to test cosmetics, could be enriched with immune cells to better mimic the reactions of a human organism.

Another possible scenario is to use such cells to test air quality. When people breathe, their macrophages and other immune cells are the first to respond to airborne pollutants. In addition, the therapeutic effect that the cells can have: in the future, specially adapted and artificially produced immune cells can even be used to cure diseases in patients, such as cancer.

With this development, it is not surprising that pharmaceutical companies and research organizations have already shown great interest in the process and are excited about ‘tailored’ immune cells. As Nico Lachmann is happy to confirm: “This question is a clear sign that our technology has a great potential for practical use – something we are currently evaluating.”

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