| 001 | 280979 | ||
| 005 | 20250924102921.0 | ||
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| 100 | 1 | _ | |a Kruse, Sebastian |0 0000-0002-4028-1391 |b 0 |
| 245 | _ | _ | |a A versatile silica nanoparticle platform for induction of T cell responses – applied for therapeutic vaccination against HPV16 E6/E7-positive tumors in MHC-humanized mice |
| 260 | _ | _ | |a Abingdon |c 2025 |b Taylor & Franics |
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| 520 | _ | _ | |a Therapeutic vaccines represent a promising treatment option for (pre)cancerous lesions, such as human papillomavirus-induced malignancies. They act via administration of tumor-specific antigens, leading to induction of antigen-specific cytotoxic T cell responses. However, vaccination efficiency is often limited when the antigen is administered alone, due to antigen instability and inefficient uptake by antigen-presenting cells (APCs). To address these limitations, nanoparticle-based vaccine delivery systems are currently under investigation. Here, we present a novel silica nanoparticle (SiNP)-based vaccine delivery platform that can be applied for the treatment of various diseases and cancer types. We show that surface-functionalized SiNPs are non-cytotoxic and quickly taken up by APCs. Incorporation of a linker/solubilizer sequence N-terminal of the epitope allows attachment of peptides regardless of their solubility as well as efficient processing and surface presentation by APCs. Whole-body distribution studies confirmed retention of the antigen at the injection site and decelerated excretion when connected to SiNPs. Furthermore, treatment with SiNPs, especially when combined with the adjuvant poly(I:C), resulted in activation of dendritic cells capable of priming CD8+ T cells. In C57BL/6 and MHC-humanized A2.DR1 mice, the SiNP-based vaccinations induced epitope-specific CD8+ T cells. Moreover, they exhibited anti-tumor activity and provided a survival benefit in a tumor model using HPV16 E6/E7-expressing PAP-A2 cells. Thus, the novel SiNP platform represents a promising new vehicle for therapeutic vaccine delivery. |
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| 700 | 1 | _ | |a Fricke, Lia T. |0 0009-0002-9985-4227 |b 1 |
| 700 | 1 | _ | |a Zottnick, Samantha |0 0000-0002-9077-635X |b 2 |
| 700 | 1 | _ | |a Schlosser, Ann-Katrin |0 0000-0003-1269-2537 |b 3 |
| 700 | 1 | _ | |a Grabowska, Agnieszka K. |b 4 |
| 700 | 1 | _ | |a Feidt, Eva |b 5 |
| 700 | 1 | _ | |a Uhl, Philipp |0 0000-0002-8616-5599 |b 6 |
| 700 | 1 | _ | |a Junglas, Ellen |b 7 |
| 700 | 1 | _ | |a Förster, Jonas D. |0 0000-0003-3437-6738 |b 8 |
| 700 | 1 | _ | |a Blersch, Josephine |0 P:(DE-2719)9000491 |b 9 |
| 700 | 1 | _ | |a Denner, Philip |0 P:(DE-2719)2810245 |b 10 |
| 700 | 1 | _ | |a Günter, Manina |0 0009-0002-5616-2589 |b 11 |
| 700 | 1 | _ | |a Autenrieth, Stella E. |0 0000-0003-4054-9041 |b 12 |
| 700 | 1 | _ | |a Fava, Eugenio |0 P:(DE-2719)2159508 |b 13 |
| 700 | 1 | _ | |a Mier, Walter |0 0000-0002-3901-5061 |b 14 |
| 700 | 1 | _ | |a Kübelbeck, Armin |b 15 |
| 700 | 1 | _ | |a Riemer, Angelika B. |0 0000-0002-5865-0714 |b 16 |
| 773 | _ | _ | |a 10.1080/2162402X.2025.2548002 |g Vol. 14, no. 1, p. 2548002 |0 PERI:(DE-600)2645309-5 |n 1 |p 2548002 |t OncoImmunology |v 14 |y 2025 |x 2162-4011 |
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