What is CAR T-cell therapy?

CAR T-cell therapies take a personalized approach: The patient’s own immune cells, known as T-cells, are extracted, modified, multiplied, and reintroduced into the body so that the immune system can fight the cancer cells on its own. This personalized treatment approach promises greater effectiveness and fewer side effects. In addition, the treatment only needs to be administered once. However, due to its complexity and the fact that it is made by hand, it is only available in limited quantities.

Why is the production of CAR T-cells so complex and expensive?

The production of CAR T-cells is a complex process involving many sequential steps: Firstly, T‑cells are extracted from the patient’s blood. These cells must be purified, activated, and genetically modified so that they can recognize cancer cells. The modified cells are then cultured and extensively tested to ensure that they are safe and effective. All of this requires sterile production facilities, specialized equipment, and well-trained staff.

The high costs are due to expensive materials and specialized reagents, as well as the complex infrastructure and the large number of tests. In addition, each treatment is tailored specifically to the patient.

Decentralized, automated production of CAR‑T‑cells

For this reason, the Fraunhofer‑Institute for Manufacturing Engineering and Automation (IPA) has developed an automation concept for small, decentralized production systems designed to process immune cells using technology from Festo.

These modular mini-factories could, for example, be operated at university hospitals. They are largely automated and require very few specialized staff. Automation significantly reduces production times and costs, making CAR‑T‑therapies faster, more affordable, and available to more patients.

Scalability of personalized cell therapies

The mini-factories consist of various modules that the cassettes pass through in sequence. For each step of the treatment process, one cassette is required per patient, in which the T-cells undergo the necessary treatments. In the cassette used for the cell modification process step, automation components from Festo ensure precise fluid transport within a very compact space.

The cassette has a self-contained, sterile fluid system that includes all the components needed to modify the cells. The elements themselves are passive. They are operated externally when the cassette is inserted into one of the modules of the mini-factory.

Precise fluid control thanks to integrated valves

In the cell culture chamber, the T-cells are exposed to viruses that introduce genetic material containing the blueprint for so-called CAR receptors. As a result, the T-cells produce special CAR receptors and become CAR T-cells.

To do this, the various media must be dispensed precisely into the cell culture chamber, mixed there, and maintained at the correct temperature. This is handled by a diffusion-bonded manifold from Festo. The distribution block contains a channel system and connects all areas of the cassette through it. It enables precise fluid transport. Valves are integrated into the manifold and are actuated from the outside using control air to establish connections between individual components.

The fluid is moved by pushing and pulling actions using compressed air or a vacuum. Intelligently controlled compressed air allows even the smallest quantities to be precisely dosed and transported within the cassette – all within a very compact footprint. In order to reuse the cassette with other patients, only the components that have come into contact with the cells and viruses need to be replaced. The system is designed so that this can be done in just a few simple steps and outside a cleanroom.