Academic Journal
Interleukin-12 decorated nanosized semiflexible Immunofilaments enable directed targeting and augmented IFNgamma responses of natural killer cells
| العنوان: | Interleukin-12 decorated nanosized semiflexible Immunofilaments enable directed targeting and augmented IFNgamma responses of natural killer cells |
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| المؤلفون: | Weiss, L., Schluck, M., Classens, R.J.P.C., Jonge, P.K.J.D. de, Waart, A.B. van der, Nguyen, K.G., Nguyen, Tam T., Zaharoff, D.A., Malmberg, K.J., Dolstra, H., Figdor, C.G., Sohlberg, E., Hammink, R. |
| المصدر: | Acta Biomaterialia, 1, 191, pp. 386-397 |
| سنة النشر: | 2025 |
| المجموعة: | Radboud University: DSpace |
| مصطلحات موضوعية: | Laboratory Medicine - Radboud University Medical Center, Medical Biosciences - Radboud University Medical Center, Neurology - Radboud University Medical Center |
| الوصف: | Item does not contain fulltext ; Immunotherapies are a powerful strategy to treat cancer by modulating the immune system to raise an anti-tumor immune response. A prime example of immunotherapies are cytokines - small immunomodulatory molecules that are widely used to stimulate immune cells. Undirected administration of cytokines, however, can cause severe side effects, preventing the use of potent cytokines, such as Interleukin (IL)-12, which induces IFNgamma responses by cytotoxic effector lymphocytes, including NK cells. Biomaterials, like nanoparticles, can encapsulate IL-12 and accumulate at the tumor site to alleviate side effects. Yet, the released IL-12 might not be directly targeted to extracellular IL-12 receptors on the specific effector cells, thereby potentially compromising the cytokine's therapeutic efficacy. Here, we develop a polymer-based platform to target NK cells, which we call immunofilaments. Immunofilaments are nanosized linear polymers that present an anti-CD16 antibody and IL-12 effectively to NK cells and lead to synergistic NK cell activation as highlighted by an increase in TNFalpha and IFNgamma production and upregulation of multiple activation markers, including CD25, CD69, and degranulation marker CD107a. NK cell proliferation is enhanced in the presence of both anti-CD16 antibody and IL-12 compared to giving IL-12 separately. Finally, we demonstrate that the IF platform is suitable for in vivo applications, as immunofilaments readily activate human NK cells upon administration to mice. STATEMENT OF SIGNIFICANCE: IL-12 is a potent cytokine that stimulates IFNgamma responses in NK cells, which supports an anti-tumor immune response. Due to its high potency, the delivery of IL-12 needs to be highly controlled to prevent severe adverse side effects, which can be achieved by using biomaterials. This study shows that nanosized polymers termed Immunofilaments can be used to immobilize IL-12 and effectively target and activate NK cells by co-conjugation of anti-CD16 antibodies. This work ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | https://hdl.handle.net/2066/315038 |
| DOI: | 10.1016/j.actbio.2024 |
| الاتاحة: | https://hdl.handle.net/2066/315038 https://doi.org/10.1016/j.actbio.2024 |
| رقم الانضمام: | edsbas.4CD7D214 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.actbio.2024 |
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