Pharmacodynamics of adeno-associated virus 8 delivery of blinatumomab targeting CD19 for lymphoma in vitro and in vivo
MENG Yu-jing
ZHAO Zhen-yu
Abstract：Objective:To investigate the preclinical efficacy of AAV8(adeno-associated virus 8)-blinatumomab(hereinafter referred to as A-BLI)in lymphoma.Methods:AAV8-blinatumomab overexpressing CD3/CD19 was transfected into 293T cells,the expression of blinatumomab in 293T cells was detected by qPCR;the binding affinity of blinatumomab to CD3/CD19 was detected by flow cytometry;Steady-Glo® luciferase reagent was used to detect the promoting effect of blinatumomab on CD19 lymphoma cells killed by hPBMCs(human peripheral blood mononuclear cells);in vivo,the mouse humanized model was constructed,the tumor size,body weight,CD45+cell ratio,and blinatumomab concentration in peripheral blood were detected after A-BLI administration.Results:Blinatumomab was over-expressed in 293T cells transfected with A-BLI and binded to CD3/CD19,and promoted the killing of CD19-overexpressing cells by hPBMC in vitro;in vivo,a single iv administration of A-BLI inhibited the lymphoma growth in mice without affecting body weight,the percentage of CD45+cells in peripheral blood was elevated,and peripheral blood blinatumomab concentrations peaked two weeks after administration,with no decrease observed by week 7.Conclusion:In vitro,A-BLI specifically kills CD19 tumor cells by targeting CD19;in vivo,A-BLI is stably expressed for a long time,inhibiting the growth of mouse lymphomas and promoting the proliferation of CD45+cells.
Keywords：lymphomablinatumomabCD19CD3adeno-associated virus 8
Publication Date：2025-07-30
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：8( 1531-1538 )