Alyssa Crispin
Research Mentor: James Moon
Mentor Department: Pharmaceutical Sciences, Pharmacy
Author(s): Not Available
Session: Session 2 (10:00 AM – 10:50 AM)
Presentation Type: Poster 22
Abstract
Neuroinflammation is a harmful immune response in the brain that plays a major role in many serious neurological diseases, including Alzheimer’s, Parkinson’s, multiple sclerosis, and traumatic brain injury [1]. Under these conditions, immune cells, such as CD4+ T cells, enter the central nervous system (CNS) and release inflammatory signals that worsen tissue damage and disrupt normal brain function. This is due to the inflammatory signals overreacting, which can cause demyelination and neuronal death [2]. Although anti-inflammatory drugs exist, most cannot effectively cross the blood–brain barrier (BBB), a protective layer that blocks many large molecules from entering the CNS. This limitation poses a major challenge for the treatment of neuroinflammatory diseases [2]. This project explores a new strategy using engineered bispecific antibodies designed to cross the BBB and specifically target CD4+ T cells. These antibodies allow one part of the antibody to bind to transport receptors on blood vessel cells, such as the transferrin receptor or CD98hc, while the other part binds to CD4 on T cells. By using receptor-mediated transport, the antibodies can move from the bloodstream into the brain, where they may reduce harmful immune activity at injury sites. To develop this approach, there are three aims of the project. Aim 1 focuses on producing anti-CD4 antibodies by cloning CD4 variable regions into antibody backbones, expressing them in HEK cells, and purifying the resulting proteins. Aim 2 involves characterizing these antibodies using high-performance liquid chromatography and SDS-PAGE techniques to confirm protein size, purity, and stability. Aim 3 tests whether the antibodies successfully bind to CD4+ T cells in peripheral blood using immune-cell binding assays. Overall, this work intends to demonstrate a more effective method for delivering anti-inflammatory treatments to the CNS, with the potential to improve outcomes for patients with neuroinflammatory diseases. References: [1] M. Beese, “Neuroinflammation: What Many Brain Diseases Have in Common – American Brain Foundation,†American Brain Foundation, Jan. 14, 2025. https://www.americanbrainfoundation.org/what-is-neuroinflammation/ [2] S. A. Sonar and G. Lal, “Differentiation and Transmigration of CD4 T Cells in Neuroinflammation and Autoimmunity,†Frontiers in Immunology, vol. 8, Nov. 2017, doi: https://doi.org/10.3389/fimmu.2017.01695.
