TY  - JOUR
AU  - Kruse, Sebastian
AU  - Fricke, Lia T.
AU  - Zottnick, Samantha
AU  - Schlosser, Ann-Katrin
AU  - Grabowska, Agnieszka K.
AU  - Feidt, Eva
AU  - Uhl, Philipp
AU  - Junglas, Ellen
AU  - Förster, Jonas D.
AU  - Blersch, Josephine
AU  - Denner, Philip
AU  - Günter, Manina
AU  - Autenrieth, Stella E.
AU  - Fava, Eugenio
AU  - Mier, Walter
AU  - Kübelbeck, Armin
AU  - Riemer, Angelika B.
TI  - 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
JO  - OncoImmunology
VL  - 14
IS  - 1
SN  - 2162-4011
CY  - Abingdon
PB  - Taylor & Franics
M1  - DZNE-2025-01061
SP  - 2548002
PY  - 2025
AB  - 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.
LB  - PUB:(DE-HGF)16
DO  - DOI:10.1080/2162402X.2025.2548002
UR  - https://pub.dzne.de/record/280979
ER  -