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The new T cell therapy shows promise for treating COVID-19 in high-risk patients

06 December 2020

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Vasileiou S, et al. Abstract 612. Presented at: ASH Annual Meeting and Exposition (virtual meeting); 5-8 December 2020.

Disclosure: Vasileiou reports on the consultancy and research funding role of AlloVir. Please see abstracts for all relevant financial disclosures from other researchers.

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Viral-specific T-cell therapy represents proof of concept to enter clinical trials for the treatment of severe COVID-19 infection, according to study results presented at the virtual ASH Annual Meeting and Exposition.

“The impact of the COVID-19 disease has been tremendous so far, with nearly 53 million confirmed cases worldwide in November and over 10 million cases in the United States in early December,” Spyridoula Vasileiou, PhD, researchers at the Center for Cell and Gene Therapy at Baylor College of Medicine, said during the presentation. “About 20% of infected patients develop severe disease that can lead to respiratory or multi-organ failure, while older age and other comorbidities such as obesity, diabetes, and [being immunocompromised] “has been identified as a major risk factor associated with poor results,” said Vasileiou. “In particular, the death rate [among] Immune-impaired transplant patients account for 20% and treatment options have so far been limited, with only one FDA-approved antiviral agent. [Meanwhile]However, other modalities, such as plasma healing and monoclonal antibodies, have been authorized for emergency use. There is still an unmet medical need for effective treatment options. “

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Data on the protective role of T cells in those exposed to SARS-CoV-2 are increasing, with individuals with more severe cases of COVID-19 more likely to have T-cell deficits or deficiency.

Spyridoula Vasileiou, PhD

Spyridoula Vasileiou

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

Based on their previous work, this research group seeks to examine the potential for targeting COVID-19 using off-the-shelf T cells that recognize SARS-CoV-2.

As a source of protective virus-specific T cells, the researchers used peripheral blood mononuclear cells from recovered individuals who had been exposed and naturally cleared the virus using their own immune systems. To determine the specific viral proteins that induce protective T cells responsible for virus elimination, Vasileiou and colleagues examined the immunogenicity of 17 antigens and identified combinations of structural and nonstructural proteins that are immunodominant and, thus, advanced for virus-specific T cells. production in the laboratory.

Using their robust manufacturing platform, the researchers were consistently able to selectively amplify these COVID-19-specific T cells, achieving an average 9.3-fold (± 1.1) expansion of virus-specific T cells in the eight donors tested. The expanded population consisted almost entirely of CD3 + T cells (97.1%), with a combination of cytotoxic (10.2%) and CD4 + (85.5%) helper T cells whose phenotype showed a profile consistent with the capacity to virus elimination – as evidenced by expression of CD25, CD69 and CD28 – and memory potential, note the investigators.

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

“This provides preclinical evidence of the safety and potential clinical benefits associated with this over-the-counter, viral-specific T cell infusion,” he told Healio.

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

“The trial sponsored by AlloVir will be conducted in two stages,” he said. “We will undergo a run-in phase to identify the maximum tolerable dose of virus-specific T-cells, and we plan to test three different cell doses. Next, we will move on to a randomized phase, where the patient will receive either standard care only or standard care plus virus-specific T cells. The main end point is safety, but we will also examine the clinical effect of therapy using the WHO ordinal scale to assess the status of patients each day during their stay in the hospital. Finally, we will examine the immune effect and persistence of cells infused over time. This trial has recently opened and is actively recruiting patients. ”

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