Fine-tuning adaptive immunity: Signalling in experienced T cells.
Fine-tuning of adaptive immunity through targeting of experienced T cells has relevance for cancer, organ transplantation, autoimmune disease and vaccines. We are using state of the art technologies to identify novel signalling pathways in experienced T cells.
Results from the project may lead to improved cancer immunotherapy, management of graft rejection and therapy for autoimmune diseases. Insight from the project may also affect development of new vaccines.
T cell signalling and cancer immunotherapy
While cancer immunotherapies targeting cancer specific T cells have been impressively successful in some patients, these therapies are also limited by potentially life threatening adverse effects due to activation also of autoreactive T cells.
In order for T cells to work, information from the surface need to be transferred to the cell interior including the cell nucleus. This signaling process is controlled by a multitude of molecules. One of these is the enzyme Lck, which is critical for the proper functioning of T cells.
T cells may be tailored to specifically recognize cancer cells by the use of chimeric antigen receptors (CAR). These receptors anchor T cells to the surface of the tumor cells via their extracellular portion and mediate information transfer to the cell interior via their engineered intracellular domain by the Lck.
It is now clear that the currently used CARs may be improved, by adding or removing particular parts that promote Lck signaling. However, in order to generate CARs with better signaling function, more information about Lck signaling in experienced T cells is required.
We use state of the art technologies to explore molecular mechanisms for how activation of experienced T cells is regulated. Results from the project will be used to improve CAR-T cell based immunotherapies.
TSAd as a modulator of immune cell signalling
Our overall aim is to delineate the molecular function in T cells of one particular adaptor molecule. We have previously found that TSAd is a crucial modulator of the immune specific tyrosine kinases Lck and Itk. These intra cellular enzymes are potent proto-oncogenes, and a number of mechanisms have evolved to control their activity.
Currently we perform a detailed characterization of TSAd´s ability to promote molecular crosstalk between Lck and Itk and the functional consequences thereof. The research will contribute to a comprehensive understanding of how key cellular signalling molecules regulate immune cells, and this insight will open new possibilities for treatment of disease.