CAR-IMMUNOTHERAPY IS A BREAKTHROUGH IN CELL BIOLOGY AND MEDICINE

Abstract

The review article provides data on the introduction into practical healthcare of treatment methods based on the technology of using genetic products for the treatment of oncohematological and oncological diseases. The technology is based on immunotherapy using certain subpopulations of immunocompetent lymphocytes and embedded chimeric antigen receptors (CAR). The use of cytotoxicity properties of certain subpopulations of lymphocytes makes it possible to create drugs from them aimed at certain patterns of malignant cells. The article presents data starting from the concept of immunoredaction of solid tumors, describes the structure of the chimeric receptor, presents data on the technology of obtaining a chimeric receptor based on CAR-T lymphocytes and the features of the developed five generations of this drug (technology). The technological stages of T-lymphocyte therapy with chimeric antigen receptors for the treatment of patients are described. The authors focused on the description of the technology for obtaining a chimeric cellular receptor using libraries of retro- and lentivirus particles. The technological features based on the fundamental developments of scientists and biologists in obtaining vectors, the complexity of creating vectors and producing a chimeric receptor by a certain subpopulation of lymphocytes, new non-integrating lentiviral vectors and the use of revolutionary CRISPR/Cas9 technology for gene editing used in obtaining new generations of vectors are described. The authors elaborated on the technology of obtaining vectors from lentiviruses and new technological advances that are used to obtain vectors and subsequently create new variants of chimeric cellular receptors and products that are available on the world market. The experience of practical application of CAR therapy, mainly with T-lymphocytic clones with a chimeric antigen receptor in oncohematology and new promising directions for their use in the treatment of solid tumors, as well as in the treatment of autoimmune diseases and in organ and tissue transplantation are described. The prospects for immunotherapy with drugs with a chimeric antigen receptor of other subpopulations of immunocompeten cells, such as NK- and NKT lymphocytes, are presented.