Cell and Molecular Biology

Building on the initial successes of T cell-based cancer immunotherapies and expanding both their scope and variety of applications, another type of immune cell is receiving increasing attention in biomedical research: Natural killer (NK) cells.

Unlike T cells, NK cells also lend themselves to allogeneic forms of therapy as they can be safely transferred between healthy donors and cancer patients. This facilitates standardizable and cost-effective stock production, which allows the products to be retrieved according to demand.

Before allogeneic NK cells can be employed as an efficient medicine, they first have to be genetically modified and equipped with new receptors that are able to recognize cancer cells. As part of a research collaboration between the Fraunhofer IZI and Oslo University Hospital, modified T-cell receptors (TCR) are being developed that are able to recognize fragments of intracellular tumor antigens on HLA-I complexes. Compared with CAR (chimeric antigen receptor) T cells, which can only recognize surface antigens, this makes for a much broader spectrum of potential target antigens.

In order to translate pertinent research findings into clinical application as quickly as possible, process solutions for pharmaceutical production are directly considered and factored in at every stage of development. Fraunhofer institutes IZI and IPA (Institute for Manufacturing Engineering and Automation) are also contributing their experience in the fields of GMP process development and the development of automation solutions for the manufacture of cell therapeutics.

Partners
Oslo University Hospital; Fraunhofer Institute for Manufacturing Engineering and Automation IPA

Genetically engineered immune cells are revolutionizing cancer medicine. In recent years (from 2017 / 2018), the CAR-T cell treatment has established itself as an important treatment option for certain forms of leukemia and lymphoma. 

In all CAR-T cell products which have been approved so far, the immune cells are genetically modified using modified viruses. These are then used as transport vehicles to permanently integrate the genes for the therapeutically relevant CAR receptor in the target cell’s genome.  

In order to further develop this technology, Fraunhofer IZI researchers are evaluating alternative methods for genetically engineering immune cells with the aim of enhancing the safety and efficiency of treatment and developing further fields of application, e.g. in autoimmune disorders.  

The direct transfer of messenger RNA (mRNA) as a template for producing therapeutic protein molecules in target cells constitutes one of the most promising alternatives to viral gene modification. Under this approach, transporting mRNA to the target site in the body constitutes the biggest obstacle to clinical application. To overcome this challenge, the mRNA delivery via nano-carriers has been optimized to transport the “securely packed” mRNA safely and efficiently. The mRNA is then released in the interior of the cells and the production of the therapeutic molecules begins.

In addition to functionality and optimal composition, initial safety-relevant toxicity testing was carried out. The results obtained now form the basis for the next step of development – a proof-of-concept study and safety assessment in an animal model. The project is sponsored by the Federal Ministry of Education and Research.

Partner
Fraunhofer Center for Applied Nanotechnology CAN