Innowacyjna terapia CAR-T w leczeniu nowotworów hematologicznych — wybrane aspekty genetyczne i immunologiczne

Abstract

Genetic modification of T lymphocytes which can produce the expression of chimeric antigen receptor (CAR) has been used a novel option for the treatment of haematological malignancies. The results seem to be promising. Reprogrammed T cells recognize specific antigens on the surface of target cells, which in turn triggers their activation independently of MHC. Appropriate antigen selectivity and intracellular signalling facilitates killing cancer cells. The use of anti-CD19 CAR-T lymphocytes in the treatment of DLBCL and ALL has radically changed the way lymphoid neoplasms are treated, especially in patients who experience relapses or resist standard therapies. The genetic transduction involves not only CAR fusion protein modified by a retrovirus or lentivirus, but also costimulatory domains, suicide genes, and transgenes to produce additional effector molecules and CAR bispecific checkpoint inhibitors. Modern genetic engineering technologies such as TALEN or CRISPR/Cas9 are used to edit genes. Their goal is to improve the response rate and extend remission duration time, target new disease entities, reduce toxicity, and possibly create ‘universal CAR-T cells’. Potential mechanisms of CAR-T lymphocyte failure include tumor escaping from immune surveillance (e.g., by loss of CD19 expression), immunosuppressive microenvironment, depletion of CAR-T lymphocytes, or their decreased activity. This review also discusses potential toxicity and possible ways to prevent or treat dangerous or life-threatening adverse effects of the therapy.