RT journal article
T1 Specific Activation of T Cells by an ACE2-Based CAR-Like Receptor upon Recognition of SARS-CoV-2 Spike Protein
A1 González García, Pablo
A1 Muñoz Miranda, Juan Pedro
A1 Fernández Cisnal, R.
A1 Olvera Collantes, Lucía
A1 Moares Fernández, Noelia del Carmen
A1 Gabucio López, Antonio
A1 Fernández Ponce, Cecilia Matilde
A1 García Cózar, Francisco José
A2 BiomedicinaBiotecnología y Salud Pública
K1 Chimeric Antigen Receptors (CAR)
K1 COVID-19
K1 SARS-CoV-2
K1 immunotherapy
K1 CARlike receptor
AB Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agentof the Coronavirus Disease 2019 (COVID-19) pandemic, which is still a health issue worldwidemostly due to a high rate of contagiousness conferred by the high-affinity binding between cell viralreceptors, Angiotensin-Converting Enzyme 2 (ACE2) and SARS-CoV-2 Spike protein. Therapies havebeen developed that rely on the use of antibodies or the induction of their production (vaccination),but despite vaccination being still largely protective, the efficacy of antibody-based therapies waneswith the advent of new viral variants. Chimeric Antigen Receptor (CAR) therapy has shown promisefor tumors and has also been proposed for COVID-19 treatment, but as recognition of CARs stillrelies on antibody-derived sequences, they will still be hampered by the high evasion capacity of thevirus. In this manuscript, we show the results from CAR-like constructs with a recognition domainbased on the ACE2 viral receptor, whose ability to bind the virus will not wane, as Spike/ACE2interaction is pivotal for viral entry. Moreover, we have developed a CAR construct based on anaffinity-optimized ACE2 and showed that both wild-type and affinity-optimized ACE2 CARs driveactivation of a T cell line in response to SARS-CoV-2 Spike protein expressed on a pulmonary cellline. Our work sets the stage for the development of CAR-like constructs against infectious agentsthat would not be affected by viral escape mutations and could be developed as soon as the receptoris identified.
PB MDPI
SN 1422-0067
YR 2023
FD 2023-04-21
LK http://hdl.handle.net/10498/30372
UL http://hdl.handle.net/10498/30372
LA eng
NO 2020 Emergency Call for Research Projects about the SARSCoV- 2 virus and the COVID-19 disease of the Institute of Health ‘Carlos III’, Ministerio de Ciencia e Innovación, Spain, grant number COV20/00173; PAIDI 2020 Consejería de Universidades, Investigación y Tecnología, grant number P20-01293; Consejería de Salud y Familias, Junta de Andalucia, Spain, grant number PECART-0096-2020.
DS Repositorio Institucional de la Universidad de Cádiz
RD 07-nov-2026