Chimeric virus-like particles presenting tumour-associated MUC1 epitope result in high titers of specific IgG antibodies in the presence of squalene oil-in-water adjuvant: towards safe cancer immunotherapy

Abstract Background Immunotherapy is emerging as a powerful treatment approach for several types of cancers. Modulating the immune system to specifically target cancer cells while sparing healthy cells, is a very promising approach for safer therapies and increased survival of cancer patients. Tumou...

Full description

Bibliographic Details
Main Authors: Mirosława Panasiuk, Karolina Zimmer, Anna Czarnota, Magdalena Narajczyk, Grażyna Peszyńska-Sularz, Milena Chraniuk, Lilit Hovhannisyan, Sabina Żołędowska, Dawid Nidzworski, Anna J. Żaczek, Beata Gromadzka
Format: Article
Language:English
Published: BMC 2022-03-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:https://doi.org/10.1186/s12951-022-01357-1
_version_ 1828115712439222272
author Mirosława Panasiuk
Karolina Zimmer
Anna Czarnota
Magdalena Narajczyk
Grażyna Peszyńska-Sularz
Milena Chraniuk
Lilit Hovhannisyan
Sabina Żołędowska
Dawid Nidzworski
Anna J. Żaczek
Beata Gromadzka
author_facet Mirosława Panasiuk
Karolina Zimmer
Anna Czarnota
Magdalena Narajczyk
Grażyna Peszyńska-Sularz
Milena Chraniuk
Lilit Hovhannisyan
Sabina Żołędowska
Dawid Nidzworski
Anna J. Żaczek
Beata Gromadzka
author_sort Mirosława Panasiuk
collection DOAJ
description Abstract Background Immunotherapy is emerging as a powerful treatment approach for several types of cancers. Modulating the immune system to specifically target cancer cells while sparing healthy cells, is a very promising approach for safer therapies and increased survival of cancer patients. Tumour-associated antigens are favorable targets for cancer immunotherapy, as they are exclusively expressed by the cancer cells, minimizing the risk of an autoimmune reaction. The ability to initiate the activation of the immune system can be achieved by virus-like particles (VLPs) which are safe and potent delivery tools. VLP‐based vaccines have evolved dramatically over the last few decades and showed great potential in preventing infectious diseases. Immunogenic potency of engineered VLPs as a platform for the development of effective therapeutic cancer vaccines has been studied extensively. This study involves recombinant VLPs presenting multiple copies of tumour-specific mucin 1 (MUC1) epitope as a potentially powerful tool for future immunotherapy. Results In this report VLPs based on the structural protein of Norovirus (NoV VP1) were genetically modified to present multiple copies of tumour-specific MUC1 epitope on their surface. Chimeric MUC1 particles were produced in the eukaryotic Leishmania tarentolae expression system and used in combination with squalene oil-in-water emulsion MF59 adjuvant to immunize BALB/c mice. Sera from vaccinated mice demonstrated high titers of IgG and IgM antibodies which were specifically recognizing MUC1 antigen. Conclusions The obtained results show that immunization with recombinant chimeric NoV VP1- MUC1 VLPs result in high titers of MUC1 specific IgG antibodies and show great therapeutic potential as a platform to present tumour-associated antigens. Graphical Abstract
first_indexed 2024-04-11T12:45:41Z
format Article
id doaj.art-e0040c6254a245bb9d66a79b77e57b05
institution Directory Open Access Journal
issn 1477-3155
language English
last_indexed 2024-04-11T12:45:41Z
publishDate 2022-03-01
publisher BMC
record_format Article
series Journal of Nanobiotechnology
spelling doaj.art-e0040c6254a245bb9d66a79b77e57b052022-12-22T04:23:23ZengBMCJournal of Nanobiotechnology1477-31552022-03-0120111310.1186/s12951-022-01357-1Chimeric virus-like particles presenting tumour-associated MUC1 epitope result in high titers of specific IgG antibodies in the presence of squalene oil-in-water adjuvant: towards safe cancer immunotherapyMirosława Panasiuk0Karolina Zimmer1Anna Czarnota2Magdalena Narajczyk3Grażyna Peszyńska-Sularz4Milena Chraniuk5Lilit Hovhannisyan6Sabina Żołędowska7Dawid Nidzworski8Anna J. Żaczek9Beata Gromadzka10Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of GdańskIntercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of GdańskIntercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of GdańskLaboratory of Electron Microscopy, Faculty of Biology, University of GdańskTri-City Central Animal Laboratory Research and Service Center, Medical University of GdańskDepartment of in vitro Studies, Institute of Biotechnology and Molecular MedicineDepartment of in vitro Studies, Institute of Biotechnology and Molecular MedicineInstitute of Biotechnology and Molecular MedicineInstitute of Biotechnology and Molecular MedicineLaboratory of Translational Oncology, Medical University of GdańskIntercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of GdańskAbstract Background Immunotherapy is emerging as a powerful treatment approach for several types of cancers. Modulating the immune system to specifically target cancer cells while sparing healthy cells, is a very promising approach for safer therapies and increased survival of cancer patients. Tumour-associated antigens are favorable targets for cancer immunotherapy, as they are exclusively expressed by the cancer cells, minimizing the risk of an autoimmune reaction. The ability to initiate the activation of the immune system can be achieved by virus-like particles (VLPs) which are safe and potent delivery tools. VLP‐based vaccines have evolved dramatically over the last few decades and showed great potential in preventing infectious diseases. Immunogenic potency of engineered VLPs as a platform for the development of effective therapeutic cancer vaccines has been studied extensively. This study involves recombinant VLPs presenting multiple copies of tumour-specific mucin 1 (MUC1) epitope as a potentially powerful tool for future immunotherapy. Results In this report VLPs based on the structural protein of Norovirus (NoV VP1) were genetically modified to present multiple copies of tumour-specific MUC1 epitope on their surface. Chimeric MUC1 particles were produced in the eukaryotic Leishmania tarentolae expression system and used in combination with squalene oil-in-water emulsion MF59 adjuvant to immunize BALB/c mice. Sera from vaccinated mice demonstrated high titers of IgG and IgM antibodies which were specifically recognizing MUC1 antigen. Conclusions The obtained results show that immunization with recombinant chimeric NoV VP1- MUC1 VLPs result in high titers of MUC1 specific IgG antibodies and show great therapeutic potential as a platform to present tumour-associated antigens. Graphical Abstracthttps://doi.org/10.1186/s12951-022-01357-1Cancer immunotherapyCancer vaccinesVLPsBioengineered nanostructuresMUC1
spellingShingle Mirosława Panasiuk
Karolina Zimmer
Anna Czarnota
Magdalena Narajczyk
Grażyna Peszyńska-Sularz
Milena Chraniuk
Lilit Hovhannisyan
Sabina Żołędowska
Dawid Nidzworski
Anna J. Żaczek
Beata Gromadzka
Chimeric virus-like particles presenting tumour-associated MUC1 epitope result in high titers of specific IgG antibodies in the presence of squalene oil-in-water adjuvant: towards safe cancer immunotherapy
Journal of Nanobiotechnology
Cancer immunotherapy
Cancer vaccines
VLPs
Bioengineered nanostructures
MUC1
title Chimeric virus-like particles presenting tumour-associated MUC1 epitope result in high titers of specific IgG antibodies in the presence of squalene oil-in-water adjuvant: towards safe cancer immunotherapy
title_full Chimeric virus-like particles presenting tumour-associated MUC1 epitope result in high titers of specific IgG antibodies in the presence of squalene oil-in-water adjuvant: towards safe cancer immunotherapy
title_fullStr Chimeric virus-like particles presenting tumour-associated MUC1 epitope result in high titers of specific IgG antibodies in the presence of squalene oil-in-water adjuvant: towards safe cancer immunotherapy
title_full_unstemmed Chimeric virus-like particles presenting tumour-associated MUC1 epitope result in high titers of specific IgG antibodies in the presence of squalene oil-in-water adjuvant: towards safe cancer immunotherapy
title_short Chimeric virus-like particles presenting tumour-associated MUC1 epitope result in high titers of specific IgG antibodies in the presence of squalene oil-in-water adjuvant: towards safe cancer immunotherapy
title_sort chimeric virus like particles presenting tumour associated muc1 epitope result in high titers of specific igg antibodies in the presence of squalene oil in water adjuvant towards safe cancer immunotherapy
topic Cancer immunotherapy
Cancer vaccines
VLPs
Bioengineered nanostructures
MUC1
url https://doi.org/10.1186/s12951-022-01357-1
work_keys_str_mv AT mirosławapanasiuk chimericviruslikeparticlespresentingtumourassociatedmuc1epitoperesultinhightitersofspecificiggantibodiesinthepresenceofsqualeneoilinwateradjuvanttowardssafecancerimmunotherapy
AT karolinazimmer chimericviruslikeparticlespresentingtumourassociatedmuc1epitoperesultinhightitersofspecificiggantibodiesinthepresenceofsqualeneoilinwateradjuvanttowardssafecancerimmunotherapy
AT annaczarnota chimericviruslikeparticlespresentingtumourassociatedmuc1epitoperesultinhightitersofspecificiggantibodiesinthepresenceofsqualeneoilinwateradjuvanttowardssafecancerimmunotherapy
AT magdalenanarajczyk chimericviruslikeparticlespresentingtumourassociatedmuc1epitoperesultinhightitersofspecificiggantibodiesinthepresenceofsqualeneoilinwateradjuvanttowardssafecancerimmunotherapy
AT grazynapeszynskasularz chimericviruslikeparticlespresentingtumourassociatedmuc1epitoperesultinhightitersofspecificiggantibodiesinthepresenceofsqualeneoilinwateradjuvanttowardssafecancerimmunotherapy
AT milenachraniuk chimericviruslikeparticlespresentingtumourassociatedmuc1epitoperesultinhightitersofspecificiggantibodiesinthepresenceofsqualeneoilinwateradjuvanttowardssafecancerimmunotherapy
AT lilithovhannisyan chimericviruslikeparticlespresentingtumourassociatedmuc1epitoperesultinhightitersofspecificiggantibodiesinthepresenceofsqualeneoilinwateradjuvanttowardssafecancerimmunotherapy
AT sabinazołedowska chimericviruslikeparticlespresentingtumourassociatedmuc1epitoperesultinhightitersofspecificiggantibodiesinthepresenceofsqualeneoilinwateradjuvanttowardssafecancerimmunotherapy
AT dawidnidzworski chimericviruslikeparticlespresentingtumourassociatedmuc1epitoperesultinhightitersofspecificiggantibodiesinthepresenceofsqualeneoilinwateradjuvanttowardssafecancerimmunotherapy
AT annajzaczek chimericviruslikeparticlespresentingtumourassociatedmuc1epitoperesultinhightitersofspecificiggantibodiesinthepresenceofsqualeneoilinwateradjuvanttowardssafecancerimmunotherapy
AT beatagromadzka chimericviruslikeparticlespresentingtumourassociatedmuc1epitoperesultinhightitersofspecificiggantibodiesinthepresenceofsqualeneoilinwateradjuvanttowardssafecancerimmunotherapy