Fraunhofer Institute for Cell Therapy and Immunology IZIGMP Development
Combined cancer immunotherapy
A tumor cell is recognized and then destroyed by a CAR-positive NK Cell via the link using the ICE molecules.
The launch of CAR-T cell therapy to treat various cancers constitutes an important milestone for the use of cellular immunotherapy in oncology.
Apart from the high hopes that this promising treatment option will become available for various types of cancer as soon as possible, the increasing numbers of patients, in turn, are also connected with various challenges. One of these is that CAR-T cell products have to be tailored to the individual patient in a complex production process, resulting in limited availability and high treatment costs.
Therefore, international research efforts are focusing on alternative immunotherapies, in addition to optimized production processes.
Natural killer cells (NK cells) are considered a promising resource to optimize the cost-efficiency and availability of cancer immunotherapies. CAR-NK cells are genetically engineered according to the same principle as CAR-T cells to enable them to find and destroy tumor cells. Unlike T cells, NK cells are not immunogenic. This means, they can also be transferred from healthy donors to patients without triggering immunological rejection. As a result, NK and CAR-NK cell products can be produced more cost efficiently and on a larger scale.
Fraunhofer IZI has examined the potential of a combination treatment comprising NK cell products and so-called innate cell engagers (ICE) on behalf of Affimed GmbH (Mannheim).
These ICE molecules attach to both NK cells and tumor cells by binding to the CD16A receptor on the immune cells and a specific antigen (CD19) on the tumor cells. As soon as this bridge is created, the immune cell is activated and destroys the tumor cell.
In this project, the antitumor effectiveness of two combination treatments (NK cells and CAR-NK cells each combined with ICE) was examined in various in vitro experiments compared with the simple CAR-NK cell treatment. This showed that the cytotoxic potential of the combination treatment is superior to the simple version. Apart from this, a significant difference was not observed between the two combinations (NK cell + ICE vs. CAR-NK cell + ICE). The use of ICE in combination with an NK cell treatment has the potential for successful cancer immunotherapy. However, this potential now has to be examined in further pre-clinical and clinical studies.