Posters
Presenting Author Academic/Professional Position
Medical Student
Academic Level (Author 1)
Medical Student
Academic Level (Author 2)
Graduate Student
Discipline/Specialty (Author 2)
Immunology and Microbiology
Presentation Type
Poster
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
This proposal outlines a project aimed at developing a novel therapeutic strategy for treating primary central nervous system diffuse large B-cell lymphoma (CNS-DLBCL) by utilizing a CD20-targeting nanobody conjugated with honokiol, a natural NF-κB inhibitor. CNS-DLBCL is an aggressive malignancy restricted to the brain and spinal cord, with poor prognosis largely due to the challenges of crossing the blood-brain barrier (BBB) and therapy resistance driven by constitutive NF-κB signaling. Honokiol, a bioactive compound derived from magnolia leaves, is capable of penetrating the BBB and inhibiting NF-κB signaling, making it an ideal candidate for targeted therapeutic intervention. The project will generate an anti-CD20 nanobody by immunizing alpacas with recombinant CD20 protein, isolating peripheral blood lymphocytes, and employing phage display screening to identify high-affinity binders. Selected nanobodies will be conjugated with honokiol via PEGylation to preserve pharmaceutical stability and activity. The honokiol-conjugated nanobody will be evaluated in vitro using CNS-DLBCL cell lines. NF-κB activity will be measured through phosphorylated IκBα and p65 levels using Western blotting and ELISA assays. Cell viability and proliferation will be assessed using MTT assays, and results will be compared with controls treated with free honokiol, unconjugated nanobody, or BAY 11-7082, a known NF-κB inhibitor. In vivo efficacy will be tested in a CNS-DLBCL xenograft mouse model. Mice will receive honokiol-conjugated nanobody treatments via optimized delivery routes. Tumor growth, NF-κB activity, and apoptosis markers will be monitored through immunohistochemistry and Western blotting. This project aims to combine the specificity of nanobody-based targeting with the therapeutic potential of honokiol to overcome the challenges posed by BBB penetration and NF-κB-mediated resistance in CNS-DLBCL. This cost-effective therapeutic strategy has the potential to improve global accessibility to lymphoma treatments, particularly in resource-limited settings. Nanobody stability and honokiol's affordability could facilitate distribution in remote areas, addressing global health disparities. If funded, this project will follow the outlined procedure to address current therapeutic limitations in CNS-DLBCL treatment and provide a foundation for future translational research.
Recommended Citation
Heckman, Justin Z. and Villa, Sophia, "Development of an NF-κB Inhibiting Nanobody-Honokiol Conjugate for Targeting Central Nervous System Diffuse Large B-Cell Lymphoma" (2025). Research Symposium. 86.
https://scholarworks.utrgv.edu/somrs/2025/posters/86
Included in
Development of an NF-κB Inhibiting Nanobody-Honokiol Conjugate for Targeting Central Nervous System Diffuse Large B-Cell Lymphoma
This proposal outlines a project aimed at developing a novel therapeutic strategy for treating primary central nervous system diffuse large B-cell lymphoma (CNS-DLBCL) by utilizing a CD20-targeting nanobody conjugated with honokiol, a natural NF-κB inhibitor. CNS-DLBCL is an aggressive malignancy restricted to the brain and spinal cord, with poor prognosis largely due to the challenges of crossing the blood-brain barrier (BBB) and therapy resistance driven by constitutive NF-κB signaling. Honokiol, a bioactive compound derived from magnolia leaves, is capable of penetrating the BBB and inhibiting NF-κB signaling, making it an ideal candidate for targeted therapeutic intervention. The project will generate an anti-CD20 nanobody by immunizing alpacas with recombinant CD20 protein, isolating peripheral blood lymphocytes, and employing phage display screening to identify high-affinity binders. Selected nanobodies will be conjugated with honokiol via PEGylation to preserve pharmaceutical stability and activity. The honokiol-conjugated nanobody will be evaluated in vitro using CNS-DLBCL cell lines. NF-κB activity will be measured through phosphorylated IκBα and p65 levels using Western blotting and ELISA assays. Cell viability and proliferation will be assessed using MTT assays, and results will be compared with controls treated with free honokiol, unconjugated nanobody, or BAY 11-7082, a known NF-κB inhibitor. In vivo efficacy will be tested in a CNS-DLBCL xenograft mouse model. Mice will receive honokiol-conjugated nanobody treatments via optimized delivery routes. Tumor growth, NF-κB activity, and apoptosis markers will be monitored through immunohistochemistry and Western blotting. This project aims to combine the specificity of nanobody-based targeting with the therapeutic potential of honokiol to overcome the challenges posed by BBB penetration and NF-κB-mediated resistance in CNS-DLBCL. This cost-effective therapeutic strategy has the potential to improve global accessibility to lymphoma treatments, particularly in resource-limited settings. Nanobody stability and honokiol's affordability could facilitate distribution in remote areas, addressing global health disparities. If funded, this project will follow the outlined procedure to address current therapeutic limitations in CNS-DLBCL treatment and provide a foundation for future translational research.
