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
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 o...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2025-12-01
|
| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2548002 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849222197195833344 |
|---|---|
| author | Sebastian Kruse Lia T. Fricke Samantha Zottnick Ann-Katrin Schlosser Agnieszka K. Grabowska Eva Feidt Philipp Uhl Ellen Junglas Jonas D. Förster Josephine Blersch Philip Denner Manina Günter Stella E. Autenrieth Eugenio Fava Walter Mier Armin Kübelbeck Angelika B. Riemer |
| author_facet | Sebastian Kruse Lia T. Fricke Samantha Zottnick Ann-Katrin Schlosser Agnieszka K. Grabowska Eva Feidt Philipp Uhl Ellen Junglas Jonas D. Förster Josephine Blersch Philip Denner Manina Günter Stella E. Autenrieth Eugenio Fava Walter Mier Armin Kübelbeck Angelika B. Riemer |
| author_sort | Sebastian Kruse |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-167bc0a3fcad4bc2b8b76a4af8867490 |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-167bc0a3fcad4bc2b8b76a4af88674902025-08-26T06:26:38ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2548002A versatile silica nanoparticle platform for induction of T cell responses – applied for therapeutic vaccination against HPV16 E6/E7-positive tumors in MHC-humanized miceSebastian Kruse0Lia T. Fricke1Samantha Zottnick2Ann-Katrin Schlosser3Agnieszka K. Grabowska4Eva Feidt5Philipp Uhl6Ellen Junglas7Jonas D. Förster8Josephine Blersch9Philip Denner10Manina Günter11Stella E. Autenrieth12Eugenio Fava13Walter Mier14Armin Kübelbeck15Angelika B. Riemer16Division of Immunotherapy & Immunoprevention, German Cancer Research Center (DKFZ), Heidelberg, GermanyDivision of Immunotherapy & Immunoprevention, German Cancer Research Center (DKFZ), Heidelberg, GermanyDivision of Immunotherapy & Immunoprevention, German Cancer Research Center (DKFZ), Heidelberg, GermanyDivision of Immunotherapy & Immunoprevention, German Cancer Research Center (DKFZ), Heidelberg, GermanySILVACX, Life Science Inkubator GmbH, Bonn, GermanySILVACX, Life Science Inkubator GmbH, Bonn, GermanyInstitute of Pharmacy and Molecular Biotechnology, Department of Pharmaceutical Technology and Biopharmacy, Heidelberg University, Heidelberg, GermanySILVACX, Life Science Inkubator GmbH, Bonn, GermanyDivision of Immunotherapy & Immunoprevention, German Cancer Research Center (DKFZ), Heidelberg, GermanyLaboratory Automation Technologies (CRFS-LAT), German Center for Neurodegenerative Diseases (DZNE), Bonn, GermanyLaboratory Automation Technologies (CRFS-LAT), German Center for Neurodegenerative Diseases (DZNE), Bonn, GermanyDendritic Cells in Infection and Cancer, German Cancer Research Center (DKFZ), Heidelberg, GermanyDendritic Cells in Infection and Cancer, German Cancer Research Center (DKFZ), Heidelberg, GermanyLaboratory Automation Technologies (CRFS-LAT), German Center for Neurodegenerative Diseases (DZNE), Bonn, GermanyDepartment of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, GermanySILVACX, Life Science Inkubator GmbH, Bonn, GermanyDivision of Immunotherapy & Immunoprevention, German Cancer Research Center (DKFZ), Heidelberg, GermanyTherapeutic 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.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2548002Amorphous silica nanoparticlescervical cancertherapeutic vaccinationMHC-humanized mouse modelA2.DR1human papillomavirus (HPV) |
| spellingShingle | Sebastian Kruse Lia T. Fricke Samantha Zottnick Ann-Katrin Schlosser Agnieszka K. Grabowska Eva Feidt Philipp Uhl Ellen Junglas Jonas D. Förster Josephine Blersch Philip Denner Manina Günter Stella E. Autenrieth Eugenio Fava Walter Mier Armin Kübelbeck Angelika B. Riemer 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 OncoImmunology Amorphous silica nanoparticles cervical cancer therapeutic vaccination MHC-humanized mouse model A2.DR1 human papillomavirus (HPV) |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | versatile silica nanoparticle platform for induction of t cell responses applied for therapeutic vaccination against hpv16 e6 e7 positive tumors in mhc humanized mice |
| topic | Amorphous silica nanoparticles cervical cancer therapeutic vaccination MHC-humanized mouse model A2.DR1 human papillomavirus (HPV) |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2548002 |
| work_keys_str_mv | AT sebastiankruse aversatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT liatfricke aversatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT samanthazottnick aversatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT annkatrinschlosser aversatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT agnieszkakgrabowska aversatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT evafeidt aversatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT philippuhl aversatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT ellenjunglas aversatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT jonasdforster aversatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT josephineblersch aversatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT philipdenner aversatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT maninagunter aversatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT stellaeautenrieth aversatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT eugeniofava aversatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT waltermier aversatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT arminkubelbeck aversatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT angelikabriemer aversatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT sebastiankruse versatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT liatfricke versatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT samanthazottnick versatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT annkatrinschlosser versatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT agnieszkakgrabowska versatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT evafeidt versatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT philippuhl versatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT ellenjunglas versatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT jonasdforster versatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT josephineblersch versatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT philipdenner versatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT maninagunter versatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT stellaeautenrieth versatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT eugeniofava versatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT waltermier versatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT arminkubelbeck versatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice AT angelikabriemer versatilesilicananoparticleplatformforinductionoftcellresponsesappliedfortherapeuticvaccinationagainsthpv16e6e7positivetumorsinmhchumanizedmice |