In vivo pharmacodynamics of two CD19-targeting CAR-T cells immunotherapy

doi:10.19803/j.1672-8629.2022.08.02

Abstract

Abstract: Objective To evaluate the efficacy of two CD19-targeting chimeric antigen receptor gene modified T cells (CAR-T) in tumor-bearing immunodeficient mice so as to provide a reference for the in vivo pharmacodynamics evaluation of related products. Methods Firefly luciferase-labeled Raji cell (Raji-Luc) xenograft model was established in B-NDG mice, and both cell A and cell B (compared with cell A, on the basis of expressing the CAR structure, cell B express the IL-6 silencer fragment to interfere with the expression of IL-6) were administered for single time on this basis, and continuedly observed until 84 days after administration. The survival rate, clinical symptoms, body weight changes, fluorescence intensity of Raji-Luc cells in vivo and histopathological changes of mice were investigated. Results Both cell A and cell B could significantly prolong the survival time of tumor-bearing mice, slow down the weight loss caused by Raji-Luc cells to a certain extent, effectively alleviate the clinical manifestations caused by the loading of Raji-Luc cells, and significantly reduce Raji-luc in vivo. The fluorescence intensity of cells significantly reduced the incidence of lymphoma in various tissues and organs of Raji-Luc cell model animals, and the changes were dose-related. Conclusion The cause of death of animals in the CAR-T treatment group may be related to the continuous consumption of the tumor and the progressively worsening background lesions. Both cell A and cell B showed a certain pharmacodynamic effect in Raji-Luc tumor-bearing B-NDG mice, and there was no significant difference in the pharmacodynamics.

Key words: chimeric antigen receptor T(CAR-T) cells, pharmacodynamic studies, targeting CD19, in vivo imaging, immuno-deficient mice, Raji-Luc cell

CLC Number:

R994
R979.1

WEN Hairuo, HUANG Ying, QU Zhe, QIN Chao, WANG Sanlong, LOU Xiaoyan, GENG Xingchao, YU Lei. In vivo pharmacodynamics of two CD19-targeting CAR-T cells immunotherapy[J]. Chinese Journal of Pharmacovigilance, 2022, 19(8): 817-822.

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