Trypanosoma cruzi as an effective cancer antigen delivery vector
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/8765 |
Resumo: | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia e Departamento de Parasitologia. Belo Horizonte, MG, Brazil/ Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil |
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Junqueira, CarolineSantos, Luara Isabela dosGalvão Filho, BrunoTeixeira, Santuza Maria RibeiroRodrigues, Flávia GuimarãesRocha, Wanderson Duarte daChiari, EglerJungbluth, Achim A.Ritter, GerdGnjatic, SachaOld, Lloyd J.Gazzinelli, Ricardo Tostes2014-11-07T13:17:36Z2014-11-07T13:17:36Z2011JUNQUEIRA, C. e al. Trypanosoma cruzi as an effective cancer antigen delivery vector. Proc Natl Acad Sci USA, 108(49): 19695-19700, 2011.0027-8424https://www.arca.fiocruz.br/handle/icict/8765engNational Academy of Sciences of the United States of AmericaTrypanosoma cruzi as an effective cancer antigen delivery vectorinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia e Departamento de Parasitologia. Belo Horizonte, MG, Brazil/ Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia e Departamento de Parasitologia. Belo Horizonte, MG, Brazil/ Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia e Departamento de Parasitologia. Belo Horizonte, MG, Brazil/ Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia e Departamento de Parasitologia. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, BrazilUniversidade Federal do Paraná. Centro Politécnico. Setor de Ciências Biológicas. Departamento de Bioquímica e Biologia Molecular. Curitiba, Paraná, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia e Departamento de Parasitologia. Belo Horizonte, MG, BrazilNew York Branch at Memorial Sloan-Kettering Cancer Center. Ludwig Institute for Cancer Research. New York, NYNew York Branch at Memorial Sloan-Kettering Cancer Center. Ludwig Institute for Cancer Research. New York, NYNew York Branch at Memorial Sloan-Kettering Cancer Center. Ludwig Institute for Cancer Research. New York, NYUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia e Departamento de Parasitologia. Belo Horizonte, MG, Brazil/ Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil/University of Massachusetts Medical School. Division of Infectious Disease and Immunology. Worcester, MAOne of the main challenges in cancer research is the development of vaccines that induce effective and long-lived protective immunity against tumors. Significant progress has been made in identifying members of the cancer testis antigen family as potential vaccine candidates. However, an ideal form for antigen delivery that induces robust and sustainable antigen-specific T-cell responses, and in particular of CD8+ T lymphocytes, remains to be developed. Here we report the use of a recombinant nonpathogenic clone of Trypanosoma cruzi as a vaccine vector to induce vigorous and longterm T cell-mediated immunity. The rationale for using the highly attenuated T. cruzi clone was (i) the ability of the parasite to persist in host tissues and therefore to induce a long-term antigen-specific immune response; (ii) the existence of intrinsic parasite agonists for Toll-like receptors and consequent induction of highly polarized T helper cell type 1 responses; and (iii) the parasite replication in the host cell cytoplasm, leading to direct antigen presentation through the endogenous pathway and consequent induction of antigenspecific CD8+ T cells. Importantly, we found that parasites expressing a cancer testis antigen (NY-ESO-1) were able to elicit human antigen-specific T-cell responses in vitro and solid protection against melanoma in a mouse model. Furthermore, in a therapeutic protocol, the parasites expressing NY-ESO-1 delayed the rate of tumor development in mice. We conclude that the T. cruzi vector is highly efficient in inducing T cell-mediated immunity and protection against cancer cells. More broadly, this strategy could be used to elicit a long-term T cell-mediated immunity and used for prophylaxis or therapy of chronic infectious diseases.cytokineprophylaxisprotozoainnate immunityTrypanosoma cruzi CL-14info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-81914https://www.arca.fiocruz.br/bitstream/icict/8765/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALTrypanosoma cruzi as an effective cancer antigen delivery vector.pdfTrypanosoma cruzi as an effective cancer antigen delivery vector.pdfapplication/pdf865170https://www.arca.fiocruz.br/bitstream/icict/8765/2/Trypanosoma%20cruzi%20as%20an%20effective%20cancer%20antigen%20delivery%20vector.pdf48dc6fd7fd067453a69f02d14c45d0b3MD52TEXTTrypanosoma cruzi as an effective cancer antigen delivery vector.pdf.txtTrypanosoma cruzi as an effective cancer antigen delivery vector.pdf.txtExtracted texttext/plain41393https://www.arca.fiocruz.br/bitstream/icict/8765/3/Trypanosoma%20cruzi%20as%20an%20effective%20cancer%20antigen%20delivery%20vector.pdf.txt138f16e62f4fd3009a4f56fe7ad42d4bMD53icict/87652019-06-19 10:12:33.952oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352019-06-19T13:12:33Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
dc.title.pt_BR.fl_str_mv |
Trypanosoma cruzi as an effective cancer antigen delivery vector |
title |
Trypanosoma cruzi as an effective cancer antigen delivery vector |
spellingShingle |
Trypanosoma cruzi as an effective cancer antigen delivery vector Junqueira, Caroline cytokine prophylaxis protozoa innate immunity Trypanosoma cruzi CL-14 |
title_short |
Trypanosoma cruzi as an effective cancer antigen delivery vector |
title_full |
Trypanosoma cruzi as an effective cancer antigen delivery vector |
title_fullStr |
Trypanosoma cruzi as an effective cancer antigen delivery vector |
title_full_unstemmed |
Trypanosoma cruzi as an effective cancer antigen delivery vector |
title_sort |
Trypanosoma cruzi as an effective cancer antigen delivery vector |
author |
Junqueira, Caroline |
author_facet |
Junqueira, Caroline Santos, Luara Isabela dos Galvão Filho, Bruno Teixeira, Santuza Maria Ribeiro Rodrigues, Flávia Guimarães Rocha, Wanderson Duarte da Chiari, Egler Jungbluth, Achim A. Ritter, Gerd Gnjatic, Sacha Old, Lloyd J. Gazzinelli, Ricardo Tostes |
author_role |
author |
author2 |
Santos, Luara Isabela dos Galvão Filho, Bruno Teixeira, Santuza Maria Ribeiro Rodrigues, Flávia Guimarães Rocha, Wanderson Duarte da Chiari, Egler Jungbluth, Achim A. Ritter, Gerd Gnjatic, Sacha Old, Lloyd J. Gazzinelli, Ricardo Tostes |
author2_role |
author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Junqueira, Caroline Santos, Luara Isabela dos Galvão Filho, Bruno Teixeira, Santuza Maria Ribeiro Rodrigues, Flávia Guimarães Rocha, Wanderson Duarte da Chiari, Egler Jungbluth, Achim A. Ritter, Gerd Gnjatic, Sacha Old, Lloyd J. Gazzinelli, Ricardo Tostes |
dc.subject.en.pt_BR.fl_str_mv |
cytokine prophylaxis protozoa innate immunity Trypanosoma cruzi CL-14 |
topic |
cytokine prophylaxis protozoa innate immunity Trypanosoma cruzi CL-14 |
description |
Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia e Departamento de Parasitologia. Belo Horizonte, MG, Brazil/ Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunopatologia. Belo Horizonte, MG, Brazil |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011 |
dc.date.accessioned.fl_str_mv |
2014-11-07T13:17:36Z |
dc.date.available.fl_str_mv |
2014-11-07T13:17:36Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
JUNQUEIRA, C. e al. Trypanosoma cruzi as an effective cancer antigen delivery vector. Proc Natl Acad Sci USA, 108(49): 19695-19700, 2011. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/8765 |
dc.identifier.issn.none.fl_str_mv |
0027-8424 |
identifier_str_mv |
JUNQUEIRA, C. e al. Trypanosoma cruzi as an effective cancer antigen delivery vector. Proc Natl Acad Sci USA, 108(49): 19695-19700, 2011. 0027-8424 |
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https://www.arca.fiocruz.br/handle/icict/8765 |
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eng |
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eng |
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openAccess |
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National Academy of Sciences of the United States of America |
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National Academy of Sciences of the United States of America |
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