SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 trial.

Despite advances, few therapeutics have shown efficacy in severe coronavirus disease 2019 (COVID-19). In a different context, virus-specific T cells have proven safe and effective. We conducted a randomized (2:1), open-label, phase 1/2 trial to evaluate the safety and efficacy of off-the-shelf, partially human leukocyte antigen (HLA)-matched, convalescent donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells (CoV-2-STs) in combination with standard of care (SoC) in patients with severe COVID-19 compared to SoC during Delta variant predominance. After a dose-escalated phase 1 safety study, 90 participants were randomized to receive CoV-2-ST+SoC (n = 60) or SoC only (n = 30). The co-primary objectives of the study were the composite of time to recovery and 30-d recovery rate and the in vivo expansion of CoV-2-STs in patients receiving CoV-2-ST+SoC over SoC. The key secondary objective was survival on day 60. CoV-2-ST+SoC treatment was safe and well tolerated. The study met the primary composite endpoint (CoV-2-ST+SoC versus SoC: recovery rate 65% versus 38%, P = 0.017; median recovery time 11 d versus not reached, P = 0.052, respectively; rate ratio for recovery 1.71 (95% confidence interval 1.03-2.83, P = 0.036)) and the co-primary objective of significant CoV-2-ST expansion compared to SοC (CoV-2-ST+SoC versus SoC, P = 0.047). Overall, in hospitalized patients with severe COVID-19, adoptive immunotherapy with CoV-2-STs was feasible and safe. Larger trials are needed to strengthen the preliminary evidence of clinical benefit in severe COVID-19. EudraCT identifier: 2021-001022-22 .

Pathogen-specific T Cells: Targeting Old Enemies and New Invaders in Transplantation and Beyond.

Adoptive immunotherapy with virus-specific cytotoxic T cells (VSTs) has evolved over the last three decades as a strategy to rapidly restore virus-specific immunity to prevent or treat viral diseases after solid organ or allogeneic hematopoietic cell-transplantation (allo-HCT). Since the early proof-of-principle studies demonstrating that seropositive donor-derived T cells, specific for the commonest pathogens post transplantation, namely cytomegalovirus or Epstein-Barr virus (EBV) and generated by time- and labor-intensive protocols, could effectively control viral infections, major breakthroughs have then streamlined the manufacturing process of pathogen-specific T cells (pSTs), broadened the breadth of target recognition to even include novel emerging pathogens and enabled off-the-shelf administration or pathogen-naive donor pST production. We herein review the journey of evolution of adoptive immunotherapy with nonengineered, natural pSTs against infections and virus-associated malignancies in the transplant setting and briefly touch upon recent achievements using pSTs outside this context.

Light vehicle regulated and unregulated emissions from different biodiesels.

In this study, the regulated and unregulated emissions profile and fuel consumption of an automotive diesel and biodiesel blends, prepared from two different biodiesels, were investigated. The biodiesels were a rapeseed methyl ester (RME) and a palm-based methyl ester (PME). The tests were performed on a chassis dynamometer with constant volume sampling (CVS) over the New European Driving Cycle (NEDC) and the non-legislated Athens Driving Cycle (ADC), using a Euro 2 compliant passenger vehicle. The objectives were to evaluate the impact of biodiesel chemical structure on the emissions, as well as the influence of the applied driving cycle on the formation of exhaust emissions and fuel consumption. The results showed that NO(x) emissions were influenced by certain biodiesel properties, such as those of cetane number and iodine number. NO(x) emissions followed a decreasing trend over both cycles, where the most beneficial reduction was obtained with the application of the more saturated biodiesel. PM emissions were decreased with the palm-based biodiesel blends over both cycles, with the exception of the 20% blend which was higher compared to diesel fuel. PME blends led to increases in PM emissions over the ADC. The majority of the biodiesel blends showed a tendency for lower CO and HC emissions. The differences in CO(2) emissions were not statistically significant. Fuel consumption presented an increase with both biodiesels. Total PAH and nitro-PAH emission levels were decreased with the use of biodiesel independently of the source material. Lower molecular weight PAHs were predominant in both gaseous and particulate phases. Both biodiesels had a negative impact on certain carbonyl emissions. Formaldehyde and acetaldehyde were the dominant aldehydes emitted from both fuels.