NFAT Family of Transcription Factors

Macián, Fernando

doi:10.1007/978-3-030-57401-7_216

Cited by 1 publication

(1 citation statement)

References 53 publications

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“…Moreover, TPR cells have already been validated and used to evaluate CAR activity [45][46][47]. We have used NFκB and NFAT and not AP-1 reporters, since AP-1 activation can most efficiently be monitor in T cells by the NFAT reporter, as the human distal ARRE-2 site from the IL-2 promoter used as NFAT reporter in TPR cells is dependent on cooperative binding of NFAT and AP-1 and therefore has no activity upon NFAT activation in the absence of AP-1 [48][49][50].…”

Section: Discussionmentioning

confidence: 99%

Specific Activation of T Cells by an ACE2-Based CAR-Like Receptor upon Recognition of SARS-CoV-2 Spike Protein

Gonzalez-Garcia

Muñoz-Miranda

Fernández-Cisnal

et al. 2023

IJMS

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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.

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