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Dendritic cell vaccines containing lymphocytes produce improved immunogenicity in patients with cancer

BACKGROUND: Dendritic cells are currently under investigation for their ability to generate anti-cancer immune responses. No consensus has been reached as to the optimal method of dendritic cell vaccine preparation and is a barrier to success in the field. METHODS: Over a course of three separate de...

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Autores principales: Frank, Mayu O, Kaufman, Julia, Parveen, Salina, Blachère, Nathalie E, Orange, Dana E, Darnell, Robert B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264264/
https://www.ncbi.nlm.nih.gov/pubmed/25475068
http://dx.doi.org/10.1186/s12967-014-0338-3
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author Frank, Mayu O
Kaufman, Julia
Parveen, Salina
Blachère, Nathalie E
Orange, Dana E
Darnell, Robert B
author_facet Frank, Mayu O
Kaufman, Julia
Parveen, Salina
Blachère, Nathalie E
Orange, Dana E
Darnell, Robert B
author_sort Frank, Mayu O
collection PubMed
description BACKGROUND: Dendritic cells are currently under investigation for their ability to generate anti-cancer immune responses. No consensus has been reached as to the optimal method of dendritic cell vaccine preparation and is a barrier to success in the field. METHODS: Over a course of three separate dendritic cell vaccine studies to treat cancer, we tested two different methods for preparing dendritic cells from peripheral blood mononuclear cells: adherence and antibody-selected CD14+ cells. RESULTS: Surprisingly, we found that patients who received dendritic cell vaccines generated by the adherence method mounted increased T cell proliferation in response to vaccination. This difference could not be accounted for by dendritic cell vaccine dose, cell surface phenotype or dendritic cell function in vitro. One notable difference between the two vaccine preparation methods was that the dendritic cell vaccine cultures generated by the adherence method contained up to 10% lymphocytes, and these lymphocytes were proliferating and producing IFNγ in response to antigen in vitro at the time of administration. CONCLUSIONS: Enhanced immunogenicity of adherence dendritic cell vaccinations may be due to the presence of lymphocytes during dendritic cell culture. TRIAL REGISTRATION: Clinicaltrials.gov identifiers: NCT00289341, NCT00345293, and NCT00893945 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-014-0338-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-42642642014-12-13 Dendritic cell vaccines containing lymphocytes produce improved immunogenicity in patients with cancer Frank, Mayu O Kaufman, Julia Parveen, Salina Blachère, Nathalie E Orange, Dana E Darnell, Robert B J Transl Med Research BACKGROUND: Dendritic cells are currently under investigation for their ability to generate anti-cancer immune responses. No consensus has been reached as to the optimal method of dendritic cell vaccine preparation and is a barrier to success in the field. METHODS: Over a course of three separate dendritic cell vaccine studies to treat cancer, we tested two different methods for preparing dendritic cells from peripheral blood mononuclear cells: adherence and antibody-selected CD14+ cells. RESULTS: Surprisingly, we found that patients who received dendritic cell vaccines generated by the adherence method mounted increased T cell proliferation in response to vaccination. This difference could not be accounted for by dendritic cell vaccine dose, cell surface phenotype or dendritic cell function in vitro. One notable difference between the two vaccine preparation methods was that the dendritic cell vaccine cultures generated by the adherence method contained up to 10% lymphocytes, and these lymphocytes were proliferating and producing IFNγ in response to antigen in vitro at the time of administration. CONCLUSIONS: Enhanced immunogenicity of adherence dendritic cell vaccinations may be due to the presence of lymphocytes during dendritic cell culture. TRIAL REGISTRATION: Clinicaltrials.gov identifiers: NCT00289341, NCT00345293, and NCT00893945 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-014-0338-3) contains supplementary material, which is available to authorized users. BioMed Central 2014-12-05 /pmc/articles/PMC4264264/ /pubmed/25475068 http://dx.doi.org/10.1186/s12967-014-0338-3 Text en © Frank et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Frank, Mayu O
Kaufman, Julia
Parveen, Salina
Blachère, Nathalie E
Orange, Dana E
Darnell, Robert B
Dendritic cell vaccines containing lymphocytes produce improved immunogenicity in patients with cancer
title Dendritic cell vaccines containing lymphocytes produce improved immunogenicity in patients with cancer
title_full Dendritic cell vaccines containing lymphocytes produce improved immunogenicity in patients with cancer
title_fullStr Dendritic cell vaccines containing lymphocytes produce improved immunogenicity in patients with cancer
title_full_unstemmed Dendritic cell vaccines containing lymphocytes produce improved immunogenicity in patients with cancer
title_short Dendritic cell vaccines containing lymphocytes produce improved immunogenicity in patients with cancer
title_sort dendritic cell vaccines containing lymphocytes produce improved immunogenicity in patients with cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264264/
https://www.ncbi.nlm.nih.gov/pubmed/25475068
http://dx.doi.org/10.1186/s12967-014-0338-3
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