New T-cell therapy shows promise for the treatment of COVID-19 in high-risk patients



December 6, 2020

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Source / publication

Source:

Vasileiou S, et al. Abstract 612. Presented at: ASH Annual Meeting and Exposition; December 5 – 8, 2020

Disclosure:
Vasileiou mentions the role of consultant and research funding from AlloVir. Relevant financial data of all other researchers can be found in the abstract.


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According to the results of a study presented at the virtual annual meeting and ASH exhibition, classical virus-specific T-cell therapy demonstrated evidence of the concept of entering a clinical trial for the treatment of severe COVID-19 infection.

“The impact of COVID-19 has been huge so far, with nearly 53 million confirmed cases worldwide since November and more than 10 million cases in the United States in early December.” Spyridoula Vasileiou, PhD, said during the presentation a researcher at the Center for Cell and Gene Therapy at Baylor College of Medicine. “Approximately 20% of infected patients develop a serious illness that can lead to respiratory or multiorgan failure, while older age and other comorbidities such as obesity, diabetes and [being immunocompromised] were identified as the main risk factors associated with poor results, “said Vasileiou. “Specifically, the mortality rate.” [among] Immunocompromised transplant patients were up to 20% and treatment options are still limited, with only one FDA-approved antiviral. [Meanwhile], emergency modalities such as convalescent plasma and monoclonal antibodies have been authorized for emergency use. The medical need for effective treatment options remains unmet. “

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The data increase on the protective role of T cells in individuals exposed to SARS-CoV-2, with individuals with more severe cases of COVID-19 more likely to have T-cell deficits or deficiencies.

Spyridoula Vasileiou, PhD

Spyridoula Vasileiou

Vasileiou and colleagues have previously demonstrated the feasibility, safety, and clinical activity of commonly available virus-specific T cells for the treatment of viral infections and / or diseases associated with a variety of viruses, including BK virus, cytomegalovirus, and others.

Based on their previous work, this group of researchers sought to explore the potential of targeting COVID-19 using common T cells that recognized SARS-CoV-2.

As a source of protective virus-specific T cells, the researchers used peripheral blood mononuclear cells from convalescents who were exposed to the virus and naturally purified it using their own immune system. In order to determine which specific viral proteins induced these protective T cells responsible for virus elimination, Vasileiou and colleagues examined the immunogenicity of 17 antigens and identified a combination of structural and nonstructural proteins that were immunodominant and therefore advanced for virus-specific T cells. laboratories.

Using their robust manufacturing platform, the researchers were consistently able to selectively amplify these COVID-19-specific T cells and achieve an average 9.3-fold (± 1.1) expansion of virus-specific T cells in the eight donors tested. The expanded populations contained almost exclusively CD3 + T cells (97.1%), with a combination of cytotoxic CD8 + (10.2%) and helper CD4 + (85.5%) T cells, whose phenotype showed a profile corresponding to viral elimination capacity – both is evidenced by the expression of CD25, CD69 and CD28 – and memory potential, the researchers said.

“When we examined the effector profile of reactive cells, we found that they were polyclonal, polyfunctional, and cytolytic against viral targets without autoreactivity or alloreactivity,” Vasileiou said.

“This provides preclinical evidence of the safety and potential clinical benefit associated with infusing these commonly available virus-specific T cells,” said Healio.

Vasileiou and colleagues are now conducting a randomized, single-center, dose-finding, evidence-of-concept study to assess the safety and efficacy of COVID-19 virus-specific T cell therapy in 40 high-risk patients.

“The process, which is sponsored by AlloVir, will take place in two phases,” she said. “We will have a run-in phase to identify the maximum tolerated dose of virus-specific T cells and plan to test three different doses of cells.” We then proceed to a randomized phase, where patients receive either standard care alone or standard care plus virus-specific T cells. The primary endpoint will be safety, but we will also examine the clinical effect of therapy using the WHO ordinal scale to assess the patient’s condition on a daily basis during hospitalization. Finally, we examine the immune effects and persistence of the infused cells over time. This study was recently launched and actively recruited patients. ”


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