A NASAL spray containing an anti-CD3 monoclonal antibody has shown promising results in ameliorating traumatic brain injury (TBI) in a mouse model, reducing central nervous system damage and improving behavioural outcomes.
Traumatic brain injury is a leading cause of death and disability worldwide, with neuroinflammation playing a crucial role in both damage and recovery processes. Currently, there are no effective therapies to mitigate CNS injury and promote recovery after TBI. Researchers at Mass General Brigham have investigated the potential of a nasal anti-CD3 monoclonal antibody as a novel therapeutic approach for TBI treatment.
The study, published in Nature Neuroscience, utilised a mouse model of contusional TBI to examine the effects of nasal anti-CD3 administration. The researchers found that the treatment induced a population of interleukin-10 (IL-10) producing regulatory T cells (Treg cells) that migrated to the brain and interacted with microglia. These Treg cells reduced chronic microglial inflammation and regulated their phagocytic function in an IL-10-dependent manner. Blocking the IL-10 receptor globally or specifically on microglia in vivo negated the beneficial effects of nasal anti-CD3. However, adoptive transfer of IL-10-producing Treg cells to TBI-injured mice restored these beneficial effects by enhancing microglial phagocytic capacity and reducing microglia-induced neuroinflammation.
These findings suggest that nasal anti-CD3 represents a promising new therapeutic approach for treating TBI and potentially other forms of acute brain injury. The next step is to translate these preclinical findings to human patients. Researchers envision potential applications ranging from treating severe TBI cases to addressing repetitive concussions in athletes. While further research is needed, this study opens up new avenues for TBI treatment and highlights the potential of immunomodulatory approaches in addressing neurological injuries.
Katrina Thornber, EMJ
Reference
Izzy S et al. Nasal anti-CD3 monoclonal antibody ameliorates traumatic brain injury, enhances microglial phagocytosis and reduces neuroinflammation via IL-10-dependent Treg–microglia crosstalk. Nature Neuroscience. 2025;DOI:10.1038/s41593-025-01877-7.
