Non-viral TRAC-knocked-in CD19^KICAR-T and gp350^KICAR-T cells tested against Burkitt lymphomas with type 1 or 2 EBV infection: In vivo cellular dynamics and potency.

ABSTRACT:

Introduction

The ubiquitous Epstein-Barr virus (EBV) is an oncogenic herpes virus associated with several human malignancies. EBV is an immune-evasive pathogen that promotes CD8⁺ T cell exhaustion and dysregulates CD4⁺ T cell functions. Burkitt lymphoma (BL) is frequently associated with EBV infections. Since BL relapses after conventional therapies are difficult to treat, we evaluated prospective off-the-shelf edited CAR-T cell therapies targeting CD19 or the EBV gp350 cell surface antigen.

Methods

We used CRISPR/Cas9 gene editing methods to knock in (KI) the CD19CAR.CD28z or gp350CAR.CD28z into the T cell receptor (TCR) alpha chain (TRAC) locus.

Results

Applying upscaled methods with the ExPERT ATx^® MaxCyte system, KI efficacy

SUBMITTER: Braun T 

PROVIDER: S-EPMC10081580 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature