Nasal administration of the fully human anti-CD3 monoclonal antibody Foralumab modulated T cell inflammatory responses in COVID-19.

Nasal administration of the monoclonal antibody Foralumab was proven to decrease inflammatory markers of COVID-19 disease.

A pilot study by Brigham and Women’s Hospital found nasal administration of the fully human anti-CD3 monoclonal antibody (mAb) modulated T cell inflammatory responses in COVID-19 by suppressing effector features in multiple T cell subsets. Notably, this result was seen in Foralumab patients with multiple sclerosis as well as in healthy patients.

An overactive immune system is a signature in COVID-19 and multiple sclerosis. Foralumab stimulates regulatory T cells of the immune system to decrease inflammation. This mode of action is unique among COVID-19 mAbs, which mostly treat or prevent symptoms by targeting the ever-evolving COVID-19 spike protein.

The investigators found evidence that Foralumab dampened inflammatory T cell response and decreased lung inflammation in COVID-19 patients. Foralumab also reduced serum IL-6 and C-reactive protein for moderate COVID-19 infections.

The study was published this week in the Proceedings of the National Academy of Sciences. Brigham and Women’s Hospital (BWH) investigators used serum proteomics and RNA sequencing to examine the immune changes in patients treated with nasal Foralumab.

Mild-to-moderate COVID-19 outpatients were randomly assigned to nasal Foralumab (100 μg/d), administered for 10 consecutive days. The investigators found that naïve-like T cells were increased in the Foralumab-treated participants, and NGK7+ effector T cells were reduced.

Because this same gene expression modulation was observed in patients with brain inflammation due to multiple sclerosis, the investigations postulate nasally administered Foralumab may demonstrate efficacy against multiple inflammatory diseases.

“We discovered a way to shut down inflammation not only seen in COVID-19, but also in a patient with multiple sclerosis as well as in healthy patients,” said lead author Thais Moreira, PhD, an assistant scientist in neurologic diseases at BWH, and a neurology instructor at Harvard Medical School. “This is very exciting because not only does our study suggest that this new monoclonal antibody drug is safe and can modulate the immune system without major side effects, but it can also decrease inflammation in multiple realms, so it may be useful for treating other diseases.”

The study authors believe nasal administration is uniquely promising in its ability to combat inflammation. “Immunomodulation by nasal anti-CD3 mAb represents a novel avenue for treatment of inflammatory human diseases,” they wrote.

Foralumab is manufactured by Tiziana Life Sciences. Next steps for this agent include a placebo-controlled double-blind trial in a larger cohort with progressive multiple sclerosis. Additionally, a new trial of Foralumab to treat long COVID is in the pipeline.

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