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Vaccination with nanoparticles combined with micro-adjuvants protects against cancer

BACKGROUND: Induction of strong T cell responses, in particular cytotoxic T cells, is a key for the generation of efficacious therapeutic cancer vaccines which yet, remains a major challenge for the vaccine developing world. Here we demonstrate that it is possible to harness the physiological proper...

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Autores principales: Mohsen, Mona O., Heath, Matthew D., Cabral-Miranda, Gustavo, Lipp, Cyrill, Zeltins, Andris, Sande, Marcos, Stein, Jens V., Riether, Carsten, Roesti, Elisa, Zha, Lisha, Engroff, Paul, El-Turabi, Aadil, Kundig, Thomas M., Vogel, Monique, Skinner, Murray A., Speiser, Daniel E., Knuth, Alexander, Kramer, Matthias F., Bachmann, Martin F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485085/
https://www.ncbi.nlm.nih.gov/pubmed/31027511
http://dx.doi.org/10.1186/s40425-019-0587-z
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author Mohsen, Mona O.
Heath, Matthew D.
Cabral-Miranda, Gustavo
Lipp, Cyrill
Zeltins, Andris
Sande, Marcos
Stein, Jens V.
Riether, Carsten
Roesti, Elisa
Zha, Lisha
Engroff, Paul
El-Turabi, Aadil
Kundig, Thomas M.
Vogel, Monique
Skinner, Murray A.
Speiser, Daniel E.
Knuth, Alexander
Kramer, Matthias F.
Bachmann, Martin F.
author_facet Mohsen, Mona O.
Heath, Matthew D.
Cabral-Miranda, Gustavo
Lipp, Cyrill
Zeltins, Andris
Sande, Marcos
Stein, Jens V.
Riether, Carsten
Roesti, Elisa
Zha, Lisha
Engroff, Paul
El-Turabi, Aadil
Kundig, Thomas M.
Vogel, Monique
Skinner, Murray A.
Speiser, Daniel E.
Knuth, Alexander
Kramer, Matthias F.
Bachmann, Martin F.
author_sort Mohsen, Mona O.
collection PubMed
description BACKGROUND: Induction of strong T cell responses, in particular cytotoxic T cells, is a key for the generation of efficacious therapeutic cancer vaccines which yet, remains a major challenge for the vaccine developing world. Here we demonstrate that it is possible to harness the physiological properties of the lymphatic system to optimize the induction of a protective T cell response. Indeed, the lymphatic system sharply distinguishes between nanoscale and microscale particles. The former reaches the fenestrated lymphatic system via diffusion, while the latter either need to be transported by dendritic cells or form a local depot. METHODS: Our previously developed cucumber-mosaic virus-derived nanoparticles termed (CuMV(TT)-VLPs) incorporating a universal Tetanus toxoid epitope TT830–843 were assessed for their draining kinetics using stereomicroscopic imaging. A nano-vaccine has been generated by coupling p33 epitope as a model antigen to CuMV(TT)-VLPs using bio-orthogonal Cu-free click chemistry. The CuMV(TT)-p33 nano-sized vaccine has been next formulated with the micron-sized microcrystalline tyrosine (MCT) adjuvant and the formed depot effect was studied using confocal microscopy and trafficking experiments. The immunogenicity of the nanoparticles combined with the micron-sized adjuvant was next assessed in an aggressive transplanted murine melanoma model. The obtained results were compared to other commonly used adjuvants such as B type CpGs and Alum. RESULTS: Our results showed that CuMV(TT)-VLPs can efficiently and rapidly drain into the lymphatic system due to their nano-size of ~ 30 nm. However, formulating the nanoparticles with the micron-sized MCT adjuvant of ~ 5 μM resulted in a local depot for the nanoparticles and a longer exposure time for the immune system. The preclinical nano-vaccine CuMV(TT)-p33 formulated with the micron-sized MCT adjuvant has enhanced the specific T cell response in the stringent B16F10p33 murine melanoma model. Furthermore, the micron-sized MCT adjuvant was as potent as B type CpGs and clearly superior to the commonly used Alum adjuvant when total CD8(+), specific p33 T cell response or tumour protection were assessed. CONCLUSION: The combination of nano- and micro-particles may optimally harness the physiological properties of the lymphatic system. Since the nanoparticles are well defined virus-like particles and the micron-sized adjuvant MCT has been used for decades in allergen-specific desensitization, this approach may readily be translated to the clinic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40425-019-0587-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-64850852019-05-03 Vaccination with nanoparticles combined with micro-adjuvants protects against cancer Mohsen, Mona O. Heath, Matthew D. Cabral-Miranda, Gustavo Lipp, Cyrill Zeltins, Andris Sande, Marcos Stein, Jens V. Riether, Carsten Roesti, Elisa Zha, Lisha Engroff, Paul El-Turabi, Aadil Kundig, Thomas M. Vogel, Monique Skinner, Murray A. Speiser, Daniel E. Knuth, Alexander Kramer, Matthias F. Bachmann, Martin F. J Immunother Cancer Research Article BACKGROUND: Induction of strong T cell responses, in particular cytotoxic T cells, is a key for the generation of efficacious therapeutic cancer vaccines which yet, remains a major challenge for the vaccine developing world. Here we demonstrate that it is possible to harness the physiological properties of the lymphatic system to optimize the induction of a protective T cell response. Indeed, the lymphatic system sharply distinguishes between nanoscale and microscale particles. The former reaches the fenestrated lymphatic system via diffusion, while the latter either need to be transported by dendritic cells or form a local depot. METHODS: Our previously developed cucumber-mosaic virus-derived nanoparticles termed (CuMV(TT)-VLPs) incorporating a universal Tetanus toxoid epitope TT830–843 were assessed for their draining kinetics using stereomicroscopic imaging. A nano-vaccine has been generated by coupling p33 epitope as a model antigen to CuMV(TT)-VLPs using bio-orthogonal Cu-free click chemistry. The CuMV(TT)-p33 nano-sized vaccine has been next formulated with the micron-sized microcrystalline tyrosine (MCT) adjuvant and the formed depot effect was studied using confocal microscopy and trafficking experiments. The immunogenicity of the nanoparticles combined with the micron-sized adjuvant was next assessed in an aggressive transplanted murine melanoma model. The obtained results were compared to other commonly used adjuvants such as B type CpGs and Alum. RESULTS: Our results showed that CuMV(TT)-VLPs can efficiently and rapidly drain into the lymphatic system due to their nano-size of ~ 30 nm. However, formulating the nanoparticles with the micron-sized MCT adjuvant of ~ 5 μM resulted in a local depot for the nanoparticles and a longer exposure time for the immune system. The preclinical nano-vaccine CuMV(TT)-p33 formulated with the micron-sized MCT adjuvant has enhanced the specific T cell response in the stringent B16F10p33 murine melanoma model. Furthermore, the micron-sized MCT adjuvant was as potent as B type CpGs and clearly superior to the commonly used Alum adjuvant when total CD8(+), specific p33 T cell response or tumour protection were assessed. CONCLUSION: The combination of nano- and micro-particles may optimally harness the physiological properties of the lymphatic system. Since the nanoparticles are well defined virus-like particles and the micron-sized adjuvant MCT has been used for decades in allergen-specific desensitization, this approach may readily be translated to the clinic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40425-019-0587-z) contains supplementary material, which is available to authorized users. BioMed Central 2019-04-26 /pmc/articles/PMC6485085/ /pubmed/31027511 http://dx.doi.org/10.1186/s40425-019-0587-z Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Mohsen, Mona O.
Heath, Matthew D.
Cabral-Miranda, Gustavo
Lipp, Cyrill
Zeltins, Andris
Sande, Marcos
Stein, Jens V.
Riether, Carsten
Roesti, Elisa
Zha, Lisha
Engroff, Paul
El-Turabi, Aadil
Kundig, Thomas M.
Vogel, Monique
Skinner, Murray A.
Speiser, Daniel E.
Knuth, Alexander
Kramer, Matthias F.
Bachmann, Martin F.
Vaccination with nanoparticles combined with micro-adjuvants protects against cancer
title Vaccination with nanoparticles combined with micro-adjuvants protects against cancer
title_full Vaccination with nanoparticles combined with micro-adjuvants protects against cancer
title_fullStr Vaccination with nanoparticles combined with micro-adjuvants protects against cancer
title_full_unstemmed Vaccination with nanoparticles combined with micro-adjuvants protects against cancer
title_short Vaccination with nanoparticles combined with micro-adjuvants protects against cancer
title_sort vaccination with nanoparticles combined with micro-adjuvants protects against cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485085/
https://www.ncbi.nlm.nih.gov/pubmed/31027511
http://dx.doi.org/10.1186/s40425-019-0587-z
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