Targeting SARS-CoV-2 infection through CAR-T-like bispecific T cell engagers incorporating ACE2
dc.contributor.author | Dogan, Mikail | |
dc.contributor.author | Kozhaya, Lina | |
dc.contributor.author | Placek, Lindsey | |
dc.contributor.author | Karabacak, Fatih | |
dc.contributor.author | Yigit, Mesut | |
dc.contributor.author | Unutmaz, Derya | |
dc.date.accessioned | 2023-02-21T12:34:52Z | |
dc.date.available | 2023-02-21T12:34:52Z | |
dc.date.issued | 2022-01-01 | |
dc.description.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 cells to selectively kill Spike-expressing targets. Furthermore, ACE2-Bite neutralized the pseudoviruses of SARS-CoV, SARS-CoV-2 wild-type, and variants including Delta and Omicron, as a decoy protein. Remarkably, ACE2-Bite molecule showed a higher binding and neutralization affinity to Delta and Omicron variants compared to SARS-CoV-2 wild-type Spike proteins. Conclusion. In conclusion, these results suggest the potential of this approach as a variant-proof, therapeutic strategy for future SARS-CoV-2 variants, employing both humoral and cellular arms of the adaptive immune response. | |
dc.description.issue | 10 | |
dc.description.volume | 11 | |
dc.identifier.doi | 10.1002/cti2.1421 | |
dc.identifier.uri | https://hdl.handle.net/11443/1827 | |
dc.identifier.uri | http://dx.doi.org/10.1002/cti2.1421 | |
dc.identifier.wos | WOS:000870828300001 | |
dc.publisher | WILEY | |
dc.relation.ispartof | CLINICAL \& TRANSLATIONAL IMMUNOLOGY | |
dc.subject | ACE2-Bite | |
dc.subject | CAR-T cell | |
dc.subject | COVID-19 | |
dc.subject | Delta | |
dc.subject | Omicron | |
dc.subject | SARS-CoV-2 | |
dc.title | Targeting SARS-CoV-2 infection through CAR-T-like bispecific T cell engagers incorporating ACE2 | |
dc.type | Article |
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