Anti-Cytokine Active Immunotherapy Based on Supramolecular Peptides for Alleviating IL-1β-Mediated Inflammation.
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2024-08
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IL-1β is a principal proinflammatory cytokine underlying multiple local and systemic chronic inflammatory conditions including psoriasis, rheumatoid arthritis, inflammatory bowel disease, and type 2 diabetes. Passive immunotherapies and biologic drugs targeting IL-1β, while offering significant clinical benefit, nevertheless have limitations such as significant non-response rates, induction of anti-drug antibodies, and high costs. Here, an active immunotherapy raising antibody responses against IL-1β employing self-assembling peptide nanofibers is described. The nanofibers contain defined quantities of B-cell epitopes from IL-1β and exogenous T helper epitopes and employ the Q11 self-assembling peptide platform. Without adjuvant, the nanofibers raised durable anti-IL-1β antibody responses that inhibit IL-1β activity in vitro and in vivo. In a mouse model of imiquimod-induced psoriasis, prophylactic immunizations with the nanofibers diminished symptoms of epidermal thickening. This therapeutic effect is associated with biasing the immune response toward an anti-inflammatory IgG1/Th2 phenotype and a lowered expression of proinflammatory genes in the skin. Further, anti-IL-1β nanofibers induced therapeutic immunosuppressive CD62L+ Treg cells. This technology represents a potential alternative for passive immunotherapies and other biologics for treating chronic inflammatory conditions.
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Shetty, Shamitha, Yaoying Wu, Christopher Z Lloyd, Nalini Mehta, Yining Liu, Mia E Woodruff, Tatiana Segura, Joel H Collier, et al. (2024). Anti-Cytokine Active Immunotherapy Based on Supramolecular Peptides for Alleviating IL-1β-Mediated Inflammation. Advanced healthcare materials. p. e2401444. 10.1002/adhm.202401444 Retrieved from https://hdl.handle.net/10161/31655.
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Scholars@Duke
Shamitha Ramakrishna Shetty
Tatiana Segura
Tatiana Segura is a Professor of Biomedical Engineering, Neurology, and Dermatology at Duke University. She received her B.S. degree in Bioengineering from the University of California, Berkeley (UC Berkeley) and her doctorate in Chemical Engineering from Northwestern University. She began her career in Biomaterials research during her doctoral work working with Prof. Lonnie Shea. She designed hydrogels for local non-viral gene delivery, a topic that she still works on today. She continued her Biomaterials training during her postdoctoral work with Jeffrey Hubbell. There she worked on the design of hydrogels and self-assembled polysulfides for gene delivery. She began her independent career at the University of California, Los Angeles (UCLA) in the Department of Chemical and Biomolecular Engineering reaching the title of Professor. At UCLA she participated actively in service culminating with her election as department Vice Chair and running the Graduate Program. At Duke she has continued to be heavily involved in service at the department, school, and university level. In only 5 years, she has Chaired 6 committees, and participated in at least 6 more, is the direct mentor to two young assistant professors, is the Co-director of the Center for Biotechnology and Tissue Engineering and serves as MPI of the T32 Biotechnology Training grant. Notably she is currently the Chair of the BME department Diversity Equity and Inclusion Committee.
Prof. Segura’s research is centered on biomaterials and in engineering biomaterial-soft tissue interactions to promote repair and regeneration. Together with her lab members, she designs new biomaterial interventions that can promote brain plasticity after stroke, promote scarless healing in skin wounds, induce tolerance of transplanted skin, and promote constructive immune responses after biomaterial implantation. Currently, her lab has 12 graduate students, 4 postdoctoral scholars, 2 master students, 1 plastic surgery resident, 16 undergraduate students, one high school student, and one research associate.
Professor Segura has received numerous awards and distinctions during her career, including being named a Senior Member of the National Academy of Inventors, receiving the Acta Biomaterialia Silver Medal, a CAREER Award from the National Science Foundation, a Outstanding Young Investigator Award from the American Society of Gene and Cell Therapy, and a National Scientist Development Grant from the American Heart Association. She was also named a Fellow of the American Institute for Medical and Biological Engineers (AIMBE). Professor Segura has published over 100 peer-reviewed papers and reviews and has over 10,000 citations. Her laboratory has been continuously funded since 2008 with several grants from the National Institutes of Health (NIH).
Joel Collier
The Collier Lab designs biomaterials for a range of biomedical applications, with a focus on understanding and controlling adaptive immune responses. Most materials investigated are created from molecular assemblies- proteins, peptides or bioconjugates that self-organize into useful structures such as nanofibers, gels, and particles.
These biomaterials are being developed as novel treatments for infectious diseases, cancer, wound healing, and chronic inflammation. Additionally, as these strategies are developed, basic insights into how materials engage the immune system are uncovered.
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