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An innovative plasmacytoid dendritic cell line-based cancer vaccine primes and expands antitumor T-cells in melanoma patients in a first-in-human trial
The efficacy of immune checkpoint inhibitors has been shown to depend on preexisting antitumor immunity; thus, their combination with cancer vaccines is an attractive therapeutic approach. Plasmacytoid dendritic cells (PDC) are strong inducers of antitumor responses and represent promising vaccine c...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153838/ https://www.ncbi.nlm.nih.gov/pubmed/32313721 http://dx.doi.org/10.1080/2162402X.2020.1738812 |
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author | Charles, Julie Chaperot, Laurence Hannani, Dalil Bruder Costa, Juliana Templier, Isabelle Trabelsi, Sabiha Gil, Hugo Moisan, Anaick Persoons, Virginie Hegelhofer, Harald Schir, Edith Quesada, Jean-Louis Mendoza, Christophe Aspord, Caroline Manches, Olivier Coulie, Pierre G. Khammari, Amir Dreno, Brigitte Leccia, Marie-Thérèse Plumas, Joel |
author_facet | Charles, Julie Chaperot, Laurence Hannani, Dalil Bruder Costa, Juliana Templier, Isabelle Trabelsi, Sabiha Gil, Hugo Moisan, Anaick Persoons, Virginie Hegelhofer, Harald Schir, Edith Quesada, Jean-Louis Mendoza, Christophe Aspord, Caroline Manches, Olivier Coulie, Pierre G. Khammari, Amir Dreno, Brigitte Leccia, Marie-Thérèse Plumas, Joel |
author_sort | Charles, Julie |
collection | PubMed |
description | The efficacy of immune checkpoint inhibitors has been shown to depend on preexisting antitumor immunity; thus, their combination with cancer vaccines is an attractive therapeutic approach. Plasmacytoid dendritic cells (PDC) are strong inducers of antitumor responses and represent promising vaccine candidates. We developed a cancer vaccine approach based on an allogeneic PDC line that functioned as a very potent antigen-presenting cell in pre-clinical studies. In this phase Ib clinical trial, nine patients with metastatic stage IV melanoma received up to 60 million irradiated PDC line cells loaded with 4 melanoma antigens, injected subcutaneously at weekly intervals. The primary endpoints were safety and tolerability. The vaccine was well tolerated and no serious vaccine-induced side effects were recorded. Strikingly, there was no allogeneic response toward the vaccine, but a significant increase in the frequency of circulating anti-tumor specific T lymphocytes was observed in two patients, accompanied by a switch from a naïve to memory phenotype, thus demonstrating priming of antigen-specific T-cells. Signs of clinical activity were observed, including four stable diseases according to IrRC and vitiligoïd lesions. Four patients were still alive at week 48. We also demonstrate the in vitro enhancement of specific T cell expansion induced by the synergistic combination of peptide-loaded PDC line with anti-PD-1, as compared to peptide-loaded PDC line alone. Taken together, these clinical observations demonstrate the ability of the PDC line based-vaccine to prime and expand antitumor CD8+ responses in cancer patients. Further trials should test the combination of this vaccine with immune checkpoint inhibitors. |
format | Online Article Text |
id | pubmed-7153838 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-71538382020-04-20 An innovative plasmacytoid dendritic cell line-based cancer vaccine primes and expands antitumor T-cells in melanoma patients in a first-in-human trial Charles, Julie Chaperot, Laurence Hannani, Dalil Bruder Costa, Juliana Templier, Isabelle Trabelsi, Sabiha Gil, Hugo Moisan, Anaick Persoons, Virginie Hegelhofer, Harald Schir, Edith Quesada, Jean-Louis Mendoza, Christophe Aspord, Caroline Manches, Olivier Coulie, Pierre G. Khammari, Amir Dreno, Brigitte Leccia, Marie-Thérèse Plumas, Joel Oncoimmunology Original Research The efficacy of immune checkpoint inhibitors has been shown to depend on preexisting antitumor immunity; thus, their combination with cancer vaccines is an attractive therapeutic approach. Plasmacytoid dendritic cells (PDC) are strong inducers of antitumor responses and represent promising vaccine candidates. We developed a cancer vaccine approach based on an allogeneic PDC line that functioned as a very potent antigen-presenting cell in pre-clinical studies. In this phase Ib clinical trial, nine patients with metastatic stage IV melanoma received up to 60 million irradiated PDC line cells loaded with 4 melanoma antigens, injected subcutaneously at weekly intervals. The primary endpoints were safety and tolerability. The vaccine was well tolerated and no serious vaccine-induced side effects were recorded. Strikingly, there was no allogeneic response toward the vaccine, but a significant increase in the frequency of circulating anti-tumor specific T lymphocytes was observed in two patients, accompanied by a switch from a naïve to memory phenotype, thus demonstrating priming of antigen-specific T-cells. Signs of clinical activity were observed, including four stable diseases according to IrRC and vitiligoïd lesions. Four patients were still alive at week 48. We also demonstrate the in vitro enhancement of specific T cell expansion induced by the synergistic combination of peptide-loaded PDC line with anti-PD-1, as compared to peptide-loaded PDC line alone. Taken together, these clinical observations demonstrate the ability of the PDC line based-vaccine to prime and expand antitumor CD8+ responses in cancer patients. Further trials should test the combination of this vaccine with immune checkpoint inhibitors. Taylor & Francis 2020-04-12 /pmc/articles/PMC7153838/ /pubmed/32313721 http://dx.doi.org/10.1080/2162402X.2020.1738812 Text en © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Charles, Julie Chaperot, Laurence Hannani, Dalil Bruder Costa, Juliana Templier, Isabelle Trabelsi, Sabiha Gil, Hugo Moisan, Anaick Persoons, Virginie Hegelhofer, Harald Schir, Edith Quesada, Jean-Louis Mendoza, Christophe Aspord, Caroline Manches, Olivier Coulie, Pierre G. Khammari, Amir Dreno, Brigitte Leccia, Marie-Thérèse Plumas, Joel An innovative plasmacytoid dendritic cell line-based cancer vaccine primes and expands antitumor T-cells in melanoma patients in a first-in-human trial |
title | An innovative plasmacytoid dendritic cell line-based cancer vaccine primes and expands antitumor T-cells in melanoma patients in a first-in-human trial |
title_full | An innovative plasmacytoid dendritic cell line-based cancer vaccine primes and expands antitumor T-cells in melanoma patients in a first-in-human trial |
title_fullStr | An innovative plasmacytoid dendritic cell line-based cancer vaccine primes and expands antitumor T-cells in melanoma patients in a first-in-human trial |
title_full_unstemmed | An innovative plasmacytoid dendritic cell line-based cancer vaccine primes and expands antitumor T-cells in melanoma patients in a first-in-human trial |
title_short | An innovative plasmacytoid dendritic cell line-based cancer vaccine primes and expands antitumor T-cells in melanoma patients in a first-in-human trial |
title_sort | innovative plasmacytoid dendritic cell line-based cancer vaccine primes and expands antitumor t-cells in melanoma patients in a first-in-human trial |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153838/ https://www.ncbi.nlm.nih.gov/pubmed/32313721 http://dx.doi.org/10.1080/2162402X.2020.1738812 |
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