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Relationship of vaccine efficacy to the kinetics of DC and T-cell responses induced by PLG-based cancer vaccines

Cancer vaccines are typically formulated for bolus injection and often produce short-lived immunostimulation resulting in poor temporal control over immune cell activation and weak oncolytic activity. One means of overcoming these limitations utilizes immunologically active biomaterial constructs. W...

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Autores principales: Ali, Omar A., Doherty, Edward, Mooney, David J., Emerich, Dwaine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Landes Bioscience 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548245/
https://www.ncbi.nlm.nih.gov/pubmed/23507728
http://dx.doi.org/10.4161/biom.1.1.16277
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author Ali, Omar A.
Doherty, Edward
Mooney, David J.
Emerich, Dwaine
author_facet Ali, Omar A.
Doherty, Edward
Mooney, David J.
Emerich, Dwaine
author_sort Ali, Omar A.
collection PubMed
description Cancer vaccines are typically formulated for bolus injection and often produce short-lived immunostimulation resulting in poor temporal control over immune cell activation and weak oncolytic activity. One means of overcoming these limitations utilizes immunologically active biomaterial constructs. We previously reported that antigen-laden, macroporous PLG scaffolds induce potent dendritic cell (DC) and cytotoxic T-lymphocyte (CTL) responses via the controlled signaling of inflammatory cytokines, antigen and toll-like receptor agonists. In this study, we describe the kinetics of these responses and illustrate their fundamental relationship to potent tumor rejection when implanted subcutaneously in a mouse B16 model of melanoma. By explanting scaffolds from mice at times ranging from 1–7 d, a seamless relationship was observed between the production of controlled CTL responses, tumor growth and long-term survival in both prophylactic and therapeutic models. Scaffolds must be implanted for > 7 d to augment CTL responses via the prolonged presentation of tumor antigen, and the benefits included a notable regression of established tumors. Host DC infiltration into the porous material persisted for 12 days (peaking at day 5 ~1.4 x 10(6) cells), and a sharp attenuation in DC numbers coincided with peak CD8(+) CTL infiltration at day 12 (~8 x 10(5) cells). Importantly, these PLG systems enhanced DC numbers in the draining lymph node, resulting in increased CD8(+) CTL subsets at days 10–16 of vaccination. These results indicate that material systems can finely control innate and adaptive immune cell responses to kill typically untreatable melanoma tumors and provide critical kinetic data for the design of vaccine carriers.
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spelling pubmed-35482452013-05-22 Relationship of vaccine efficacy to the kinetics of DC and T-cell responses induced by PLG-based cancer vaccines Ali, Omar A. Doherty, Edward Mooney, David J. Emerich, Dwaine Biomatter Report Cancer vaccines are typically formulated for bolus injection and often produce short-lived immunostimulation resulting in poor temporal control over immune cell activation and weak oncolytic activity. One means of overcoming these limitations utilizes immunologically active biomaterial constructs. We previously reported that antigen-laden, macroporous PLG scaffolds induce potent dendritic cell (DC) and cytotoxic T-lymphocyte (CTL) responses via the controlled signaling of inflammatory cytokines, antigen and toll-like receptor agonists. In this study, we describe the kinetics of these responses and illustrate their fundamental relationship to potent tumor rejection when implanted subcutaneously in a mouse B16 model of melanoma. By explanting scaffolds from mice at times ranging from 1–7 d, a seamless relationship was observed between the production of controlled CTL responses, tumor growth and long-term survival in both prophylactic and therapeutic models. Scaffolds must be implanted for > 7 d to augment CTL responses via the prolonged presentation of tumor antigen, and the benefits included a notable regression of established tumors. Host DC infiltration into the porous material persisted for 12 days (peaking at day 5 ~1.4 x 10(6) cells), and a sharp attenuation in DC numbers coincided with peak CD8(+) CTL infiltration at day 12 (~8 x 10(5) cells). Importantly, these PLG systems enhanced DC numbers in the draining lymph node, resulting in increased CD8(+) CTL subsets at days 10–16 of vaccination. These results indicate that material systems can finely control innate and adaptive immune cell responses to kill typically untreatable melanoma tumors and provide critical kinetic data for the design of vaccine carriers. Landes Bioscience 2011-07-01 /pmc/articles/PMC3548245/ /pubmed/23507728 http://dx.doi.org/10.4161/biom.1.1.16277 Text en Copyright © 2011 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Report
Ali, Omar A.
Doherty, Edward
Mooney, David J.
Emerich, Dwaine
Relationship of vaccine efficacy to the kinetics of DC and T-cell responses induced by PLG-based cancer vaccines
title Relationship of vaccine efficacy to the kinetics of DC and T-cell responses induced by PLG-based cancer vaccines
title_full Relationship of vaccine efficacy to the kinetics of DC and T-cell responses induced by PLG-based cancer vaccines
title_fullStr Relationship of vaccine efficacy to the kinetics of DC and T-cell responses induced by PLG-based cancer vaccines
title_full_unstemmed Relationship of vaccine efficacy to the kinetics of DC and T-cell responses induced by PLG-based cancer vaccines
title_short Relationship of vaccine efficacy to the kinetics of DC and T-cell responses induced by PLG-based cancer vaccines
title_sort relationship of vaccine efficacy to the kinetics of dc and t-cell responses induced by plg-based cancer vaccines
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548245/
https://www.ncbi.nlm.nih.gov/pubmed/23507728
http://dx.doi.org/10.4161/biom.1.1.16277
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