@misc{10498/30372,
year = {2023},
month = {4},
url = {http://hdl.handle.net/10498/30372},
abstract = {Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent
of the Coronavirus Disease 2019 (COVID-19) pandemic, which is still a health issue worldwide
mostly due to a high rate of contagiousness conferred by the high-affinity binding between cell viral
receptors, Angiotensin-Converting Enzyme 2 (ACE2) and SARS-CoV-2 Spike protein. Therapies have
been 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 wanes
with the advent of new viral variants. Chimeric Antigen Receptor (CAR) therapy has shown promise
for tumors and has also been proposed for COVID-19 treatment, but as recognition of CARs still
relies on antibody-derived sequences, they will still be hampered by the high evasion capacity of the
virus. In this manuscript, we show the results from CAR-like constructs with a recognition domain
based on the ACE2 viral receptor, whose ability to bind the virus will not wane, as Spike/ACE2
interaction is pivotal for viral entry. Moreover, we have developed a CAR construct based on an
affinity-optimized ACE2 and showed that both wild-type and affinity-optimized ACE2 CARs drive
activation of a T cell line in response to SARS-CoV-2 Spike protein expressed on a pulmonary cell
line. Our work sets the stage for the development of CAR-like constructs against infectious agents
that would not be affected by viral escape mutations and could be developed as soon as the receptor
is identified.},
organization = {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.},
publisher = {MDPI},
keywords = {Chimeric Antigen Receptors (CAR)},
keywords = {COVID-19},
keywords = {SARS-CoV-2},
keywords = {immunotherapy},
keywords = {CARlike receptor},
title = {Specific Activation of T Cells by an ACE2-Based CAR-Like Receptor upon Recognition of SARS-CoV-2 Spike Protein},
doi = {10.3390/ijms24087641},
author = {González García, Pablo and Muñoz Miranda, Juan Pedro and Fernández Cisnal, R. and Olvera Collantes, Lucía and Moares Fernández, Noelia del Carmen and Gabucio López, Antonio and Fernández Ponce, Cecilia Matilde and García Cózar, Francisco José},
}