THE SCIENTIFIC DISCUSSION OF SOME ISSUES OF FEATURES AND CHALLENGES OF USING OF CAR-T CELLS IN IMMUNOTHERAPY

Aim of the research was to study and analyze some issues of features of using of car-t cells in immunotherapy.  The characterization of CAR-T cell products involves evaluating their phenotype, genotype, and functional attributes using techniques such as flow cytometry, PCR-based assays, and cytotoxicity assays. Long-term stability studies assess product viability, potency, and cytokine secretion profiles across different storage conditions to determine shelf-life and facilitate product logistics. Biomarkers serve as crucial tools in the field of cancer immunotherapy, aiding in patient selection and treatment optimization. In the context of chimeric antigen receptor (CAR) T cell therapy, biomarkers play a significant role in predicting treatment response, identifying potential toxicities, and guiding personalized treatment approaches. Predictive biomarkers in CAR-T cell therapy commonly center on the profiles of tumor antigen expression. The selection of target antigens plays a crucial role in treatment outcomes, with higher and more consistent expression levels correlating with better response rates. The tumor microenvironment (TME) significantly influences CAR-T cell activity. Biomarkers reflecting TME features, such as immune cell infiltration, cytokine profiles, and expression of inhibitory molecules, offer insights into the immunosuppressive nature of the TME and its effects on CAR-T cell effectiveness. Patients with an inflamed TME, marked by abundant effector T cells and low expression of inhibitory molecules like PD-L1, tend to respond better to CAR-T cell therapy. CAR-T cells demonstrate bystander killing effects, where nearby tumor cells without the target antigen are eradicated via a phenomenon called antigen spreading. This process is triggered by the release of cytokines and the presentation of tumor antigens by antigen-presenting cells (APCs), resulting in the activation of the body's own immune effector cells against the tumor cells. CAR-T cells exhibit strong antitumor capabilities, they can face resistance mechanisms within the tumor microenvironment. The immunosuppressive cell populations like regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), as well as inhibitory cytokines such as transforming growth factor-beta (TGF-β) and interleukin-10 (IL-10). The resistance mechanisms, strategies involve employing combination therapies with immune checkpoint inhibitors, cytokine modulators, and targeted therapies aimed at disrupting immunosuppressive pathways. CAR-T cell therapy has revolutionized cancer treatment by harnessing the power of the immune system to target and eliminate tumor cells.