% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Kruse:280979, author = {Kruse, Sebastian and Fricke, Lia T. and Zottnick, Samantha and Schlosser, Ann-Katrin and Grabowska, Agnieszka K. and Feidt, Eva and Uhl, Philipp and Junglas, Ellen and Förster, Jonas D. and Blersch, Josephine and Denner, Philip and Günter, Manina and Autenrieth, Stella E. and Fava, Eugenio and Mier, Walter and Kübelbeck, Armin and Riemer, Angelika B.}, title = {{A} versatile silica nanoparticle platform for induction of {T} cell responses – applied for therapeutic vaccination against {HPV}16 {E}6/{E}7-positive tumors in {MHC}-humanized mice}, journal = {OncoImmunology}, volume = {14}, number = {1}, issn = {2162-4011}, address = {Abingdon}, publisher = {Taylor $\&$ Franics}, reportid = {DZNE-2025-01061}, pages = {2548002}, year = {2025}, abstract = {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.}, cin = {CRFS / LAT}, ddc = {610}, cid = {I:(DE-2719)1040000 / I:(DE-2719)1040190}, pnm = {899 - ohne Topic (POF4-899)}, pid = {G:(DE-HGF)POF4-899}, typ = {PUB:(DE-HGF)16}, doi = {10.1080/2162402X.2025.2548002}, url = {https://pub.dzne.de/record/280979}, }