Исследование фармакокинетики нового противоопухолевого препарата CAR-CEA на модели экспериментальных животных

Introduction. One of the directions of adoptive cancer immunotherapy is the use of T-lymphocytes expressing the chimeric antigen receptor (CAR) for the treatment of hemoblastosis and solid tumors. Genetic modification of lymphocytes can be achieved by transduction of retroviral genes, which leads to constitutive expression of CAR in T cells, or by electroporation of plasmid/mRNA, which leads to temporary expression of immunoreceptors, minimizing the risk of potential autoaggression and genome disturbance. We have developed the drug CAR-CEA, which is a lymphocyte modified by electroporation of plasmid DNA encoding CAR, directed against carcinoembryonic antigen (CEA). Aim – to study the pharmacokinetics of CAR–CEA with a single intravenous administration to experimental animals and to evaluate the half-life of the drug. Material and methods. The study was performed on a B6D2F1 mouse model. CAR-CEA was obtained by transfecting mouse lymphocytes with plasmid 3C1-3g electroporation, and administered intravenously at a dose of 10⁶ cells per animal. The amount of CAR-CEA in blood cells, lung, spleen and thymus tissues was assessed by PCR based on the content of plasmid DNA. The parameters of the pharmacokinetics of CAR-T were evaluated at 14 time points (30 min – 30 days). Results. The maximum concentration of CAR-CEA plasmid DNA in the whole blood of mice was determined 30 minutes after administration and was 125 ± 29 pg/ml. Further, the decrease in concentration occurred exponentially. The half-life was 105 ± 7 hours. CAR-CEA showed the ability to circulate in the bloodstream for up to a month. The most significant and prolonged accumulation of the drug was observed in the spleen. Conclusion. The results of our preclinical study show that CAR-CEA can be used for anti-СEA therapy under the condition of repeated injections.