This Team, coordinated by Professor Francisco José García Cózar, works with the virus receptor itself, which "remains effective for different strains despite mutations."

Researchers from the University of Cádiz the Cádiz Institute for Biomedical Research and Innovation Cádiz INIBICA), coordinated by Professor of Immunology Francisco García Cózar from the Department of Biomedicine, Biotechnology, and Public Health at the University of Cádiz, have been working since the pandemic began (initially funded by the COVID fund of the Carlos III Health Institute) on the development of an alternative treatment for COVID that can be applied, with some modifications, to other pandemics that may arise in the future and, in general, to serious infectious diseases.

In the early stages of a new infection, as was the case with COVID-19, and until vaccines and other specific therapies, such as monoclonal antibodies, are developed, "we find ourselves without the tools to save the lives of susceptible patients, including immunocompromised patients," explains the study's first author, Pablo González García.

In light of this, the Team experts began working on adapting CAR-T (chimeric antigen receptors in T cells) technology for COVID-19. This technology is already being used successfully to treat tumors and involves creating a DNA construct that allows us to make the most of the two types of immunity available to our defenses: antibody-based immunity and cellular immunity. "These CARs use a fragment of an antibody to identify tumor cells and other structures to cause T lymphocytes (a type of white blood cell) to kill tumor cells."

The group led by Dr. García Cózar, instead of using an antibody-based fragment to recognize cells infected by the virus, has used the virus's own receptor, ACE2, which "has the advantage of remaining effective against different strains despite any mutations the virus may undergo, because all of them have to be able to bind to the receptor to infect cells and, therefore, will have to continue to fit with this decoy receptor, which, instead of allowing itself to be killed, will eliminate the infected cells, preventing the virus from developing inside them."

On the other hand, and in view of future pandemics, a CAR can be designed for a new virus as soon as its receptor is known, information that is usually available long before effective monoclonal antibodies or vaccines are developed.

In addition to developing this therapy, these immunology experts argue that "when a virus enters our body, the immune system sometimes overreacts and causes collateral damage." In COVID-19, "this collateral damage to the lungs is responsible for much of the deterioration that occurs in seriously ill patients, which is why some patients are being treated with anti-cytokines and corticosteroids, drugs that are used in autoimmune rheumatic diseases." Based on these facts and taking into account that this group of researchers has been working for years on the development of 'chimeric' receptors that "instead of destroying what is recognized, reduce that destruction, we are also going to work on adapting the receptors against the virus to a dual function, allowing them to switch from a mode of destroying infected cells to a mode of inhibition in cases where the immune system's activity is excessive."

Referencia bibliográfica: González-García, P.; Muñoz-Miranda, J.P.; Fernández- Cisnal, R.; Olvera, L.; Moares, N.; Gabucio, A.; Fernández-Ponce, C.; García-Cozar, F. (2023): ‘Specific Activation of T Cells by an ACE2-Based CAR-like Receptor upon Recognition of SARS-CoV-2 Spike Protein’. Int. J. Mol. Sci. 24, 7641. https://doi.org/10.3390/ijms24087641.

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