Успехи молекулярной онкологии (Apr 2023)
Study of the suppression of a tumor growth expressing a carcinoembryonic antigen with a new high-tech drug carplasmin (CAR-T therapy) in Balb/c nude mice
Abstract
Introduction. Adoptive immunotherapy based on chimeric antigen receptors (CAR) is considered as a promising direction in the treatment of solid malignant tumors. To produce genetically modified human T-lymphocytes, lenti/retroviral transduction is currently most often used. However, safety concerns associated with the viral vector production and possible unwanted genome modification limit the clinical utility of CAR-T cells. Therefore, non-viral transfection methods, in particular electroporation, using of DNA or RNA vectors, are being actively studied as a method for producing CAR-T lymphocytes.Aim. To evaluate in vivo antitumor activity of the new high-tech drug carplasmin, intended for CAR-T therapy of tumors expressing carcinoembryonic antigen (CEA). Materials and methods. Carplasmin was obtained by electroporation of activated human lymphocytes with plasmid DNA carrying the third generation CAR gene specific to CEA. The study was performed on a human colorectal cancer xenograft model obtained by intraperitoneal injection of CEA-positive HCT116 cell line to athymic Balb/c nude mice. Carplasmin treatment was carried out once a week, starting from the third day after HCT116 cell inoculation. Mice in the two control groups were treated with either electroporated lymphocytes without plasmid addition (pulse-lymphocytes) or RPMI-1640 culture medium (group without treatment).Results. In vivo, carplasmin demonstrated a pronounced antitumor effect. Seven weekly injections of the drug to inoculated mice led to a prominent effect of antitumor therapy: 80 % of the animals in the experimental group survived (with 40 % of the mice had a complete remission without signs of a detectable tumor), compared to 100 % death in the control group (without treatment).Conclusion. The results of preclinical efficacy studies demonstrate that carplasmin is a promising drug for the treatment of CEA-positive intraperitoneal tumors.
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