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Immunization with nanovaccines containing mutated K-Ras peptides and imiquimod aggravates heterotopic pancreatic cancer induced in mice
PURPOSE: The growing incidence and lethality of pancreatic cancer urges the development of new therapeutic approaches. Anti-tumoral vaccines can potentiate the immune response against the tumor, targeting specific antigens expressed only on tumor cells. In this work, we designed new vaccines for pan...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10130386/ https://www.ncbi.nlm.nih.gov/pubmed/37122717 http://dx.doi.org/10.3389/fimmu.2023.1153724 |
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author | Martínez-Pérez, Amparo Diego-González, Lara Vilanova, Manuel Correia, Alexandra Simón-Vázquez, Rosana González-Fernández, África |
author_facet | Martínez-Pérez, Amparo Diego-González, Lara Vilanova, Manuel Correia, Alexandra Simón-Vázquez, Rosana González-Fernández, África |
author_sort | Martínez-Pérez, Amparo |
collection | PubMed |
description | PURPOSE: The growing incidence and lethality of pancreatic cancer urges the development of new therapeutic approaches. Anti-tumoral vaccines can potentiate the immune response against the tumor, targeting specific antigens expressed only on tumor cells. In this work, we designed new vaccines for pancreatic cancer, composed by chitosan nanocapsules (CS NCs) containing imiquimod (IMQ) as adjuvant, and targeting the K-Ras mutation G12V. EXPERIMENTAL DESIGN: We tested the immunogenicity of our vaccines in mice, carrying different combinations of K-Ras mutated peptides. Then, we analyzed their prophylactic and therapeutic efficacy in mice bearing heterotopic pancreatic cancer. RESULTS: Unexpectedly, although good results were observed at short time points, the different combinations of our CS NCs vaccines seemed to potentiate tumor growth and reduce survival rate. We propose that this effect could be due to an inadequate immune response, partially because of the induction of a regulatory tolerogenic response. CONCLUSION: Our results call for caution in the use of some NCs containing IMQ in the immunotherapy against pancreatic cancer. |
format | Online Article Text |
id | pubmed-10130386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101303862023-04-27 Immunization with nanovaccines containing mutated K-Ras peptides and imiquimod aggravates heterotopic pancreatic cancer induced in mice Martínez-Pérez, Amparo Diego-González, Lara Vilanova, Manuel Correia, Alexandra Simón-Vázquez, Rosana González-Fernández, África Front Immunol Immunology PURPOSE: The growing incidence and lethality of pancreatic cancer urges the development of new therapeutic approaches. Anti-tumoral vaccines can potentiate the immune response against the tumor, targeting specific antigens expressed only on tumor cells. In this work, we designed new vaccines for pancreatic cancer, composed by chitosan nanocapsules (CS NCs) containing imiquimod (IMQ) as adjuvant, and targeting the K-Ras mutation G12V. EXPERIMENTAL DESIGN: We tested the immunogenicity of our vaccines in mice, carrying different combinations of K-Ras mutated peptides. Then, we analyzed their prophylactic and therapeutic efficacy in mice bearing heterotopic pancreatic cancer. RESULTS: Unexpectedly, although good results were observed at short time points, the different combinations of our CS NCs vaccines seemed to potentiate tumor growth and reduce survival rate. We propose that this effect could be due to an inadequate immune response, partially because of the induction of a regulatory tolerogenic response. CONCLUSION: Our results call for caution in the use of some NCs containing IMQ in the immunotherapy against pancreatic cancer. Frontiers Media S.A. 2023-04-12 /pmc/articles/PMC10130386/ /pubmed/37122717 http://dx.doi.org/10.3389/fimmu.2023.1153724 Text en Copyright © 2023 Martínez-Pérez, Diego-González, Vilanova, Correia, Simón-Vázquez and González-Fernández https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Martínez-Pérez, Amparo Diego-González, Lara Vilanova, Manuel Correia, Alexandra Simón-Vázquez, Rosana González-Fernández, África Immunization with nanovaccines containing mutated K-Ras peptides and imiquimod aggravates heterotopic pancreatic cancer induced in mice |
title | Immunization with nanovaccines containing mutated K-Ras peptides and imiquimod aggravates heterotopic pancreatic cancer induced in mice |
title_full | Immunization with nanovaccines containing mutated K-Ras peptides and imiquimod aggravates heterotopic pancreatic cancer induced in mice |
title_fullStr | Immunization with nanovaccines containing mutated K-Ras peptides and imiquimod aggravates heterotopic pancreatic cancer induced in mice |
title_full_unstemmed | Immunization with nanovaccines containing mutated K-Ras peptides and imiquimod aggravates heterotopic pancreatic cancer induced in mice |
title_short | Immunization with nanovaccines containing mutated K-Ras peptides and imiquimod aggravates heterotopic pancreatic cancer induced in mice |
title_sort | immunization with nanovaccines containing mutated k-ras peptides and imiquimod aggravates heterotopic pancreatic cancer induced in mice |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10130386/ https://www.ncbi.nlm.nih.gov/pubmed/37122717 http://dx.doi.org/10.3389/fimmu.2023.1153724 |
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