Targeting SARS-CoV-2 infection through CAR-T-like bispecific T cell engagers incorporating ACE2.

ABSTRACT:

Objectives

Despite advances in antibody treatments and vaccines, COVID-19 caused by SARS-CoV-2 infection remains a major health problem resulting in excessive morbidity and mortality and the emergence of new variants has reduced the effectiveness of current vaccines.

Methods

Here, as a proof-of-concept, we engineered primary CD8 T cells to express SARS-CoV-2 Spike protein-specific CARs, using the extracellular region of ACE2 and demonstrated their highly specific and potent cytotoxicity towards Spike-expressing target cells. To improve on this concept as a potential therapeutic, we developed a bispecific T cell engager combining ACE2 with an anti-CD3 scFv (ACE2-Bite) to target infected cells and the virus.

Results

As in CAR-T cell approach, ACE2-Bite endowed cytotoxic

SUBMITTER: Dogan M 

PROVIDER: S-EPMC9586837 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature