Journal Article

DZNE-2025-01061

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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

Kruse, S. ; Fricke, L. T. ; Zottnick, S. ; Schlosser, A.-K. ; Grabowska, A. K. ; Feidt, E. ; Uhl, P. ; Junglas, E. ; Förster, J. D. ; Blersch, J.DZNE* ; Denner, P.DZNE* ; Günter, M. ; Autenrieth, S. E. ; Fava, E.DZNE* ; Mier, W. ; Kübelbeck, A. ; Riemer, A. B.

2025
Taylor & Franics Abingdon

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Please use a persistent id in citations: doi:10.1080/2162402X.2025.2548002

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.

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Contributing Institute(s):

1. Core Research Facilities & Services (CRFS)
2. Laboratory Automation Technologies (CRFS-LAT) (LAT)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
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