%0 Journal Article
%A Kruse, Sebastian
%A Fricke, Lia T.
%A Zottnick, Samantha
%A Schlosser, Ann-Katrin
%A Grabowska, Agnieszka K.
%A Feidt, Eva
%A Uhl, Philipp
%A Junglas, Ellen
%A Förster, Jonas D.
%A Blersch, Josephine
%A Denner, Philip
%A Günter, Manina
%A Autenrieth, Stella E.
%A Fava, Eugenio
%A Mier, Walter
%A Kübelbeck, Armin
%A Riemer, Angelika B.
%T 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
%J OncoImmunology
%V 14
%N 1
%@ 2162-4011
%C Abingdon
%I Taylor & Franics
%M DZNE-2025-01061
%P 2548002
%D 2025
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%R 10.1080/2162402X.2025.2548002
%U https://pub.dzne.de/record/280979