Point mutation in CD19 facilitates immune escape of B cell lymphoma from CAR-T cell therapy.

ABSTRACT:

Background

Tumor relapse due to mutation in CD19 can hinder the efficacy of chimeric antigen receptor (CAR)-T cell therapy. Herein, we focused on lymphoma patients whose B cells exhibited a point mutation in CD19 of B cells after CAR-T cell infusion.

Methods

The CAR-T and CD19⁺ B cells from peripheral blood or bone marrow were assessed using flow cytometry. Genome sequencing was conducted to identify the molecular characteristics of CAR-T and CD19⁺ B cells from pre-relapse and postrelapse samples. CD19 in CARs comprising single chain fragments variable (scFV) antibody with FMC63 or 21D4 was constructed. The cytotoxic efficacy of CAR-T cells was also evaluated via in vitro and in vivo experiments.

Results

A patient with high-grade B

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC7539592 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature