Cancer therapy shows potential for treatment of severe COVID-19 in preclinical trials

 Cancer therapy shows potential for treatment of severe COVID-19 in preclinical trials

An article published in Science Advances suggests that a type of cancer treatment called immune checkpoint blockade may be beneficial in some cases of severe COVID-19. The creators of the therapy, which can successfully activate the immune system to fight cancer, won the 2018 Nobel Prize in Physiology or Medicine.

The results reported by the authors were based on experiments with cells from patients treated in intensive care units (ICUs) after infection with SARS-CoV-2 and mice infected with MHV-A59 (murine hepatitis virus A59). Another beta corona virus.

"PD-1 blockade is one of the well-known immune checkpoint therapies and one of the treatments we analyzed in the study. It tells T lymphocytes [a type of white blood cell] to Stop responding to infection after a period of time so that the response is not excessive. In cases of cancer, sepsis and severe COVID-19, however, PD-1 T cells stop working before the disease resolves. is and therefore it is important to block it," said Pedro Morais-Veira, one of the study's leaders. Moraes-Vieira is a professor at the Institute of Biology (IB-UNICAMP) of the State University of Campinas in São Paulo, Brazil, and is supported by FAPESP.

Another co-author is Gustavo Gastão Davanzo, a PhD candidate at IB-UNICAMP with a scholarship from FAPESP.

"These are very expensive treatments, but we believe it could be a viable option because there are not as many critical patients as there were at the beginning of the pandemic, provided further research confirms that these are effective in treating COVID-19 patients. is safe for," Morris-Vera said.

Murine Corona Virus

The hypothesis tested in the study arose when Uruguayan researchers (co-authors of the paper) observed that mice that did not express the TMEM176D protein responded more strongly to infection with MHV-A59. This protein regulates inflammasomes, protein complexes that are deployed by the innate immune system to activate inflammation as a weapon against tumors, viruses, and bacteria.

Inflammasome activation is more severe without TMEM176D. More inflammatory cytokines are released, including interleukin-1 beta (IL-1β), which is known to play a role in acute COVID-19.

Excessive release of IL-1β leads to T-lymphocyte dysfunction, which we call T-cell exhaustion," said Maurice Vieira. "These cells are so strongly activated that they can no longer respond appropriately. This is common in chronic viral diseases such as severe COVID-19, as we found in a study conducted early in the pandemic.

An article on the study in question, published in Cell Metabolism in 2020, is one of the most cited articles published in the journal in the past three years and prompted the Uruguayan team to propose a contribution.

In trials involving mice, treatment with a PD-1 inhibitor restored T cell function. In addition, the researchers had access to blood from healthy donors and hospitalized COVID-19 patients at two institutions in Montevideo, the capital of Uruguay.

Experiments involving healthy cells infected with SARS-CoV-2 were carried out at UNICAMP's Laboratory of Emerging Virus Studies (LEVE) in collaboration with FAPESP, led by Professor José Luiz Proença Modena, co-author of the article.

In trials involving human blood samples, only cells that came from intensive care patients benefited from administration of atezolizumab, the PD-1 inhibitor used in the study. This was due to excessive activation of the inflammasome resulting in exhaustion and dysfunction of the adaptive immune system in these patients.

The researchers cautioned that the findings should be considered with caution. Studies involving cancer patients who were treated this way before contracting COVID-19 have shown no benefit or negative outcomes.

In one study, therapy administered prior to viral infection did not lead to improvement in COVID-19. In another study, involving 423 patients, there were more cases of hospitalization and severe illness among those given the inhibitor. On the other hand, clinical trials of PD-1 inhibitors in patients with sepsis showed the therapy to be safe. More research will therefore be needed to gain a deeper understanding of the treatment's effects in the context of COVID-19.

About the São Paulo Research Foundation (FAPESP).

The São Paulo Research Foundation (FAPESP) is a public institution whose mission is to support scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators affiliated with higher education and research institutions in the state of São Paulo, Brazil. FAPESP is aware that the best research can only be done by working with the best researchers at the international level. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research institutes known for the quality of its research and its grants to further promote its international collaboration. is encouraging scientists funded through You can find more information about FAPESP at www.fapesp.br/en and visit the FAPESP News Agency at www.agencia.fapesp.br/en to stay updated with the latest scientific achievements FAPESP has many of its Helps achieve through programs, awards and research centers.