RT Journal Article SR Electronic T1 Engineered chimeric T cell receptor fusion construct (TRuC)-expressing T cells prevent translational shutdown in SARS-CoV-2-infected cells JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.06.25.449871 DO 10.1101/2021.06.25.449871 A1 Ira Godbole A1 Kevin Ciminski A1 O. Sascha Yousefi A1 Salma Pathan-Chhatbar A1 Deniz Saltukoglu A1 Niklas Vesper A1 Pavel Salavei A1 Juliane Strietz A1 Nicole Gensch A1 Michael Reth A1 Martin Schwemmle A1 Wolfgang W. Schamel YR 2021 UL http://biorxiv.org/content/early/2021/06/25/2021.06.25.449871.abstract AB SARS-CoV-2, the causative agent of Covid-19, is known to evade the immune system by several mechanisms. This includes the shutdown of the host cellular protein synthesis, which abrogates the induction of antiviral interferon responses. The virus initiates the infection of susceptible cells by binding with its spike protein (S) to the host angiotensin-converting enzyme 2 (ACE2). Here we applied the T cell receptor fusion construct (TRuC) technology to engineer T cells against such infected cells. In our TRuCs an S-binding domain is fused to the CD3ε component of the T cell receptor (TCR) complex, enabling recognition of S-containing cells in an HLA independent manner. This domain either consists of the S-binding part of ACE2 or a single-chain variable fragment of an anti-S antibody. We show that the TRuC T cells are activated by and kill cells that express S of SARS-CoV-2 and its alpha (B.1.1.7) and beta (B.1.351) variants at the cell surface. Treatment of SARS-CoV-2 infected cells with our engineered T cells did not lead to massive cytotoxicity towards the infected cells, but resulted in a complete rescue of the translational shutdown despite ongoing viral replication. Our data show that engineered TRuC T cell products might be used against SARS-CoV-2 by exposing infected cells to the host innate immune system.Competing Interest StatementW.W.S. serves on the scientific advisory board of TCR2 Therapeutics. Patent application is pending.