Therapy with modified T lymphocytes (CAR-T) is one of the most modern forms of immunotherapy for cancer treatment. It is based on genetically modified, autologous T cells, which express a chimeric antigen receptor (CAR) on their surface. This receptor is able to recognize tumor antigens and trigger a T lymphocytes - mediated immune response. CAR-T cell therapy currently enables treatment of some forms of leukemia. Extensive use is limited by the complex and expensive process of making CAR-T cells, lack of known tumour target antigens, poor antitumor efficacy and survival of CAR-T cells in a toxic tumor microenvironment, and side effects of the therapy. One of the strategies to overcome these barriers is the use of genome editing on CAR-T cells. Guided nucleases such as ZFN, TALEN and the CRISPR/Cas system introduce site-specific DNA double-strand breaks in the T cell genome, activating repair mechanisms, which are used to create desired modifications of the genome. Genome edited CAR-T cells may result in more effective and safer therapies in the future. Current strategies are primarily focused on the development of allogeneic CAR-T cells, as this would simplify production and make therapy more affordable. The aim is also to identify additional tumor-specific target antigens and develop CAR-T cells with better antitumor efficacy that would maintain the ability to proliferate in vivo. In the future, we can expect new CAR-T cell therapies, which will not only be safer and more effective, but will also enable the treatment of a wider range of diseases.
|