Harnessing Allogeneic SARS-CoV-2-Specific T Cells for COVID-19 High-Risk Patient Treatment

On March 11, 2020, COVID-19 was declared a pandemic by the WHO, with nearly 17 million confirmed cases globally by July's end, including 4.5 million in the US. The disease, caused by the SARS-CoV-2 virus, can lead to severe outcomes such as respiratory distress syndrome and organ failure, with a mortality rate of up to 4%. Risk factors include advanced age, underlying health conditions like hypertension and diabetes, and weakened immune systems. High mortality rates have been noted in immunocompromised patients, such as those who have undergone hematopoietic stem cell transplantation (HSCT).

Evidence suggests that T cells play a protective role against the virus, with severe cases showing reduced T cell counts and dysregulation. A research group has shown the potential of using allogeneic, ex vivo expanded, virus-specific T cells (multi-VSTs) to treat infections in immunocompromised individuals. With the absence of effective preventative or therapeutic agents and the emerging importance of SARS-CoV-2-specific T cells, the group explored the possibility of developing a banked, SARS-CoV-2-specific VST product for high-risk individuals, such as HSCT recipients, the elderly, and those with comorbidities.

The study involved screening peripheral blood mononuclear cells (PBMCs) from individuals who had mild COVID-19 and had recovered. They tested T cell activity against a range of SARS-CoV-2 proteins, identifying eight immunodominant proteins for VST production. Using an optimized manufacturing process, they generated SARS-CoV-2-specific T cells targeting these proteins.

The results showed a significant expansion of CD3+ T cells, predominantly composed of a mix of cytotoxic and helper T cells, with characteristics suggesting effector function and memory potential. The cells expressed activation markers and showed a Th1-polarized profile, producing IFNγ and TNFα in response to the viral antigens. The cells were also capable of selectively killing targets expressing viral antigens without affecting non-antigen-expressing cells, demonstrating their selectivity and safety.

The conclusion of the study is that SARS-CoV-2 VSTs derived from recovered individuals are Th1-polarized, polyfunctional, and can selectively target and kill viral antigen-expressing cells without auto- or alloreactivity. The product is being rapidly developed for clinical trials to evaluate its effectiveness in preventing severe disease in high-risk hospitalized patients.