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Cationic nanoparticles enhance T cell tumor infiltration and antitumor immune responses to a melanoma vaccine

In clinical settings, cancer vaccines as monotherapies have displayed limited success compared to other cancer immunotherapeutic treatments. Nanoscale formulations have the ability to increase the efficacy of cancer vaccines by combatting the immunosuppressive nature of the tumor microenvironment. H...

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Autores principales: Smith, Rasheid, Wafa, Emad I., Geary, Sean M., Ebeid, Kareem, Alhaj-Suliman, Suhaila O., Salem, Aliasger K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299550/
https://www.ncbi.nlm.nih.gov/pubmed/35857851
http://dx.doi.org/10.1126/sciadv.abk3150
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author Smith, Rasheid
Wafa, Emad I.
Geary, Sean M.
Ebeid, Kareem
Alhaj-Suliman, Suhaila O.
Salem, Aliasger K.
author_facet Smith, Rasheid
Wafa, Emad I.
Geary, Sean M.
Ebeid, Kareem
Alhaj-Suliman, Suhaila O.
Salem, Aliasger K.
author_sort Smith, Rasheid
collection PubMed
description In clinical settings, cancer vaccines as monotherapies have displayed limited success compared to other cancer immunotherapeutic treatments. Nanoscale formulations have the ability to increase the efficacy of cancer vaccines by combatting the immunosuppressive nature of the tumor microenvironment. Here, we have synthesized a previously unexplored cationic polymeric nanoparticle formulation using polyamidoamine dendrimers and poly(d,l-lactic-co-glycolic acid) that demonstrate adjuvant properties in vivo. Tumor-challenged mice vaccinated with an adenovirus-based cancer vaccine [encoding tumor-associated antigen (TAA)] and subsequently treated with this nanoparticulate formulation showed significant increases in TAA-specific T cells in the peripheral blood, reduced tumor burden, protection against tumor rechallenge, and a significant increase in median survival. An investigation into cell-based pathways suggests that administration of the nanoformulation at the site of the developing tumor may have created an inflammatory environment that attracted activated TAA-specific CD8(+) T cells to the vicinity of the tumor, thus enhancing the efficacy of the vaccine.
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spelling pubmed-92995502022-08-09 Cationic nanoparticles enhance T cell tumor infiltration and antitumor immune responses to a melanoma vaccine Smith, Rasheid Wafa, Emad I. Geary, Sean M. Ebeid, Kareem Alhaj-Suliman, Suhaila O. Salem, Aliasger K. Sci Adv Biomedicine and Life Sciences In clinical settings, cancer vaccines as monotherapies have displayed limited success compared to other cancer immunotherapeutic treatments. Nanoscale formulations have the ability to increase the efficacy of cancer vaccines by combatting the immunosuppressive nature of the tumor microenvironment. Here, we have synthesized a previously unexplored cationic polymeric nanoparticle formulation using polyamidoamine dendrimers and poly(d,l-lactic-co-glycolic acid) that demonstrate adjuvant properties in vivo. Tumor-challenged mice vaccinated with an adenovirus-based cancer vaccine [encoding tumor-associated antigen (TAA)] and subsequently treated with this nanoparticulate formulation showed significant increases in TAA-specific T cells in the peripheral blood, reduced tumor burden, protection against tumor rechallenge, and a significant increase in median survival. An investigation into cell-based pathways suggests that administration of the nanoformulation at the site of the developing tumor may have created an inflammatory environment that attracted activated TAA-specific CD8(+) T cells to the vicinity of the tumor, thus enhancing the efficacy of the vaccine. American Association for the Advancement of Science 2022-07-20 /pmc/articles/PMC9299550/ /pubmed/35857851 http://dx.doi.org/10.1126/sciadv.abk3150 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Smith, Rasheid
Wafa, Emad I.
Geary, Sean M.
Ebeid, Kareem
Alhaj-Suliman, Suhaila O.
Salem, Aliasger K.
Cationic nanoparticles enhance T cell tumor infiltration and antitumor immune responses to a melanoma vaccine
title Cationic nanoparticles enhance T cell tumor infiltration and antitumor immune responses to a melanoma vaccine
title_full Cationic nanoparticles enhance T cell tumor infiltration and antitumor immune responses to a melanoma vaccine
title_fullStr Cationic nanoparticles enhance T cell tumor infiltration and antitumor immune responses to a melanoma vaccine
title_full_unstemmed Cationic nanoparticles enhance T cell tumor infiltration and antitumor immune responses to a melanoma vaccine
title_short Cationic nanoparticles enhance T cell tumor infiltration and antitumor immune responses to a melanoma vaccine
title_sort cationic nanoparticles enhance t cell tumor infiltration and antitumor immune responses to a melanoma vaccine
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299550/
https://www.ncbi.nlm.nih.gov/pubmed/35857851
http://dx.doi.org/10.1126/sciadv.abk3150
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