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A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade

BACKGROUND: The inefficacy of standard therapeutic strategies for ovarian cancer is reflected by the enduring poor prognosis of this malignancy. Due to the potential for exquisite specificity, sensitivity and long-term memory, immunotherapy offers an alternative modality for durable control of the d...

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Autores principales: Mirandola, Leonardo, Chiriva-Internati, Maurizio, Bresalier, Robert, Piccotti, Lucia, Grizzi, Fabio, Marincola, Francesco M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931250/
https://www.ncbi.nlm.nih.gov/pubmed/31878933
http://dx.doi.org/10.1186/s12967-019-02163-4
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author Mirandola, Leonardo
Chiriva-Internati, Maurizio
Bresalier, Robert
Piccotti, Lucia
Grizzi, Fabio
Marincola, Francesco M.
author_facet Mirandola, Leonardo
Chiriva-Internati, Maurizio
Bresalier, Robert
Piccotti, Lucia
Grizzi, Fabio
Marincola, Francesco M.
author_sort Mirandola, Leonardo
collection PubMed
description BACKGROUND: The inefficacy of standard therapeutic strategies for ovarian cancer is reflected by the enduring poor prognosis of this malignancy. Due to the potential for exquisite specificity, sensitivity and long-term memory, immunotherapy offers an alternative modality for durable control of the disease, provided appropriate antigens can be identified and presented in the right context. METHODS: We tested a novel dendritic cell vaccine formulation to reprogram autologous antigen-specific T-cells in vitro, in vivo in a murine model of ovarian cancer, and ex vivo using human cells from patients. RESULTS: We show that dendritic cells (DCs) treated with a p38 MAPK inhibitor and transduced with a recombinant adenovirus associated vector (AAV) expressing Sperm protein (Sp) 17 are highly effective in generating antigen-specific T-cell cytotoxic response against ovarian cancer cells. Additionally, these DCs enhanced the differentiation of effector T-cells while reducing the frequency of Foxp3(+) T-reg cells in vitro. CONCLUSIONS: This work provides a rationale for translation of pharmacologically reprogrammed DCs into clinical trials for prevention of tumor recurrence and progression in high-risk ovarian cancer patients.
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spelling pubmed-69312502019-12-30 A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade Mirandola, Leonardo Chiriva-Internati, Maurizio Bresalier, Robert Piccotti, Lucia Grizzi, Fabio Marincola, Francesco M. J Transl Med Research BACKGROUND: The inefficacy of standard therapeutic strategies for ovarian cancer is reflected by the enduring poor prognosis of this malignancy. Due to the potential for exquisite specificity, sensitivity and long-term memory, immunotherapy offers an alternative modality for durable control of the disease, provided appropriate antigens can be identified and presented in the right context. METHODS: We tested a novel dendritic cell vaccine formulation to reprogram autologous antigen-specific T-cells in vitro, in vivo in a murine model of ovarian cancer, and ex vivo using human cells from patients. RESULTS: We show that dendritic cells (DCs) treated with a p38 MAPK inhibitor and transduced with a recombinant adenovirus associated vector (AAV) expressing Sperm protein (Sp) 17 are highly effective in generating antigen-specific T-cell cytotoxic response against ovarian cancer cells. Additionally, these DCs enhanced the differentiation of effector T-cells while reducing the frequency of Foxp3(+) T-reg cells in vitro. CONCLUSIONS: This work provides a rationale for translation of pharmacologically reprogrammed DCs into clinical trials for prevention of tumor recurrence and progression in high-risk ovarian cancer patients. BioMed Central 2019-12-19 /pmc/articles/PMC6931250/ /pubmed/31878933 http://dx.doi.org/10.1186/s12967-019-02163-4 Text en © The Author(s) 2019 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.
spellingShingle Research
Mirandola, Leonardo
Chiriva-Internati, Maurizio
Bresalier, Robert
Piccotti, Lucia
Grizzi, Fabio
Marincola, Francesco M.
A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade
title A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade
title_full A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade
title_fullStr A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade
title_full_unstemmed A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade
title_short A novel method for efficient generation of antigen-specific effector T-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade
title_sort novel method for efficient generation of antigen-specific effector t-cells using dendritic cells transduced with recombinant adeno-associated virus and p38 kinase blockade
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931250/
https://www.ncbi.nlm.nih.gov/pubmed/31878933
http://dx.doi.org/10.1186/s12967-019-02163-4
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