Nanovaccine administration route is critical to obtain pertinent iNKt cell help for robust anti-tumor T and B cell responses
Nanovaccines, co-delivering antigen and invariant natural killer T (iNKT) cell agonists, proved to be very effective in inducing anti-tumor T cell responses due to their exceptional helper function. However, it is known that iNKT cells are not equally present in all lymphoid organs and nanoparticles...
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doaj-c812d3d1313e4b30b8812dcd99efb2742021-09-24T14:41:23ZengTaylor & Francis GroupOncoImmunology2162-402X2020-01-019110.1080/2162402X.2020.17388131738813Nanovaccine administration route is critical to obtain pertinent iNKt cell help for robust anti-tumor T and B cell responsesYusuf Dölen0Michael Valente1Oya Tagit2Eliezer Jäger3Eric A. W. Van Dinther4N. Koen van Riessen5Martin Hruby6Uzi Gileadi7Vincenzo Cerundolo8Carl G. Figdor9Radboud University Medical Center & Oncode InstituteRadboud University Medical Center & Oncode InstituteRadboud University Medical Center & Oncode InstituteAcademy of Sciences of the Czech RepublicRadboud University Medical Center & Oncode InstituteRadboud University Medical Center & Oncode InstituteAcademy of Sciences of the Czech RepublicUniversity of OxfordUniversity of OxfordRadboud University Medical Center & Oncode InstituteNanovaccines, co-delivering antigen and invariant natural killer T (iNKT) cell agonists, proved to be very effective in inducing anti-tumor T cell responses due to their exceptional helper function. However, it is known that iNKT cells are not equally present in all lymphoid organs and nanoparticles do not get evenly distributed to all immune compartments. In this study, we evaluated the effect of the vaccination route on iNKT cell help to T and B cell responses for the first time in an antigen and agonist co-delivery setting. Intravenous administration of PLGA nanoparticles was mainly targeting liver and spleen where iNKT1 cells are abundant and induced the highest serum IFN-y levels, T cell cytotoxicity, and Th-1 type antibody responses. In comparison, after subcutaneous or intranodal injections, nanoparticles mostly drained or remained in regional lymph nodes where iNKT17 cells were abundant. After subcutaneous and intranodal injections, antigen-specific IgG2 c production was hampered and IFN-y production, as well as cytotoxic T cell responses, depended on sporadic systemic drainage. Therapeutic anti-tumor experiments also demonstrated a clear advantage of intravenous injection over intranodal or subcutaneous vaccinations. Moreover, tumor control could be further improved by PD-1 immune checkpoint blockade after intravenous vaccination, but not by intranodal vaccination. Anti PD-1 antibody combination mainly exerts its effect by prolonging the cytotoxicity of T cells. Nanovaccines also demonstrated synergism with anti-4-1BB agonistic antibody treatment in controlling tumor growth. We conclude that nanovaccines containing iNKT cell agonists shall be preferentially administered intravenously, to optimally reach cellular partners for inducing effective anti-tumor immune responses.http://dx.doi.org/10.1080/2162402X.2020.1738813cancer vaccinesnanoparticle biodistributioninkt cellspd-14-1bbcheckpoint blockade |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yusuf Dölen Michael Valente Oya Tagit Eliezer Jäger Eric A. W. Van Dinther N. Koen van Riessen Martin Hruby Uzi Gileadi Vincenzo Cerundolo Carl G. Figdor |
spellingShingle |
Yusuf Dölen Michael Valente Oya Tagit Eliezer Jäger Eric A. W. Van Dinther N. Koen van Riessen Martin Hruby Uzi Gileadi Vincenzo Cerundolo Carl G. Figdor Nanovaccine administration route is critical to obtain pertinent iNKt cell help for robust anti-tumor T and B cell responses OncoImmunology cancer vaccines nanoparticle biodistribution inkt cells pd-1 4-1bb checkpoint blockade |
author_facet |
Yusuf Dölen Michael Valente Oya Tagit Eliezer Jäger Eric A. W. Van Dinther N. Koen van Riessen Martin Hruby Uzi Gileadi Vincenzo Cerundolo Carl G. Figdor |
author_sort |
Yusuf Dölen |
title |
Nanovaccine administration route is critical to obtain pertinent iNKt cell help for robust anti-tumor T and B cell responses |
title_short |
Nanovaccine administration route is critical to obtain pertinent iNKt cell help for robust anti-tumor T and B cell responses |
title_full |
Nanovaccine administration route is critical to obtain pertinent iNKt cell help for robust anti-tumor T and B cell responses |
title_fullStr |
Nanovaccine administration route is critical to obtain pertinent iNKt cell help for robust anti-tumor T and B cell responses |
title_full_unstemmed |
Nanovaccine administration route is critical to obtain pertinent iNKt cell help for robust anti-tumor T and B cell responses |
title_sort |
nanovaccine administration route is critical to obtain pertinent inkt cell help for robust anti-tumor t and b cell responses |
publisher |
Taylor & Francis Group |
series |
OncoImmunology |
issn |
2162-402X |
publishDate |
2020-01-01 |
description |
Nanovaccines, co-delivering antigen and invariant natural killer T (iNKT) cell agonists, proved to be very effective in inducing anti-tumor T cell responses due to their exceptional helper function. However, it is known that iNKT cells are not equally present in all lymphoid organs and nanoparticles do not get evenly distributed to all immune compartments. In this study, we evaluated the effect of the vaccination route on iNKT cell help to T and B cell responses for the first time in an antigen and agonist co-delivery setting. Intravenous administration of PLGA nanoparticles was mainly targeting liver and spleen where iNKT1 cells are abundant and induced the highest serum IFN-y levels, T cell cytotoxicity, and Th-1 type antibody responses. In comparison, after subcutaneous or intranodal injections, nanoparticles mostly drained or remained in regional lymph nodes where iNKT17 cells were abundant. After subcutaneous and intranodal injections, antigen-specific IgG2 c production was hampered and IFN-y production, as well as cytotoxic T cell responses, depended on sporadic systemic drainage. Therapeutic anti-tumor experiments also demonstrated a clear advantage of intravenous injection over intranodal or subcutaneous vaccinations. Moreover, tumor control could be further improved by PD-1 immune checkpoint blockade after intravenous vaccination, but not by intranodal vaccination. Anti PD-1 antibody combination mainly exerts its effect by prolonging the cytotoxicity of T cells. Nanovaccines also demonstrated synergism with anti-4-1BB agonistic antibody treatment in controlling tumor growth. We conclude that nanovaccines containing iNKT cell agonists shall be preferentially administered intravenously, to optimally reach cellular partners for inducing effective anti-tumor immune responses. |
topic |
cancer vaccines nanoparticle biodistribution inkt cells pd-1 4-1bb checkpoint blockade |
url |
http://dx.doi.org/10.1080/2162402X.2020.1738813 |
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