Increasing production of custom immune cells for drug development and testing

To prevent animal testing and create even more accurate ways to test therapeutics, the pharmaceutical industry is increasingly turning to human immune cells. However, the availability of cells like these has been limited to date. Now, Fraunhofer researchers have succeeded in taking the production of personalized immune cells from the laboratory to the industrial level.

Human immune cells and immune cell preparations play an increasingly important role in modern medicine – in new cancer treatments and in the development and testing of new drugs, for example. To obtain these cells for health research purposes, the industry has long relied on human donors or used cell lines from different types of cancer. However, since every human being and every cancer cell is unique, it has not been possible to standardize the processes involved. This proved to be a major problem until two stem cell researchers from Japan and the UK discovered a huge game-changer in 2006, when they succeeded in converting mature skin cells into induced pluripotent stem cells ( iPSC), which can then redevelop into different cell types. In recognition of this, Shinya Yamanaka and John B. Gurdon were awarded the 2012 Nobel Prize in Physiology or Medicine – the fastest prize ever awarded in the history of medicine.

Enter Professor Nico Lachmann and his team at the Fraunhofer Institute for Toxicology and Experimental Medicine ITEM and the Medical School Hannover (MHH), who are now harnessing the ability of these iPSCs to divide and differentiate indefinitely. Researchers have developed an unprecedented method to continuously produce specific and mature immune cells from these iPSCs in scalable systems from small to industrial-scale applications. This is done in a device resembling a large snow globe, where the stem cells are immersed in a solution and kept in constant motion. Thanks to new bioprocesses, they continuously propagate the targeted immune cells. Additionally, iPSCs do not need to be replaced for about three months to maintain consistent quality.

Large-scale immune cells

The ingenious design – in 3D, instead of the previous 2D design at the bottom of a Petri dish – is what really sets the process apart. This means that researchers are able to produce significantly larger quantities of design immune cells and the scale can be scaled up as needed. As Professor Lachmann states: “We spent three years researching the ideal medium, angle and speed for standardized production of immune cells from iPSCs and repeatedly adjusted many parameters in the process. road. This optimized method is a major asset for the study and evaluation of drugs. candidates because we can test their efficacy and safety directly in human target structures without having to resort to animal experiments, which are actually very time-consuming. »

Initially, his team specialized in macrophages, which are scavenger cells that fight bacteria and are an important part of the human immune response. The next step will see Professor Lachmann and his team establish cell-based potency tests (for cancer drugs, for example). These test systems can measure the potency of biological and bioengineered drugs and play a vital role in quality control and release testing of active ingredients and drugs. Based on their key technology for the continuous production of macrophages, the researchers also intend to develop novel manufacturing processes for various fully standardized immune cell products and cell-based immunotherapies, thereby opening up many additional applications. .

A multitude of applications

The potential for engineered immune cells is huge – to take one example, they can be genetically engineered to turn on when they detect impurities in drugs, something that has been very laborious to identify so far. The artificial skin tissue, already used to test cosmetics, could be enriched with immune cells to better reproduce the reactions of a human body. Another possible scenario would include using such cells to test air quality. When people breathe, their macrophages and other immune cells are the first to react to pollutants in the air. In addition, there is the therapeutic effect that the cells can have: in the future, specifically adapted and artificially produced immune cells could even be used to cure diseases in patients, such as cancer.

With all of this in mind, it’s no surprise that pharmaceutical companies and research organizations have already shown keen interest in the process and are excited about designing immune cells. As Nico Lachmann is happy to confirm: “This request is a clear sign that our technology has great potential for practical exploitation – something we are currently evaluating.”