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Intratumoral Combinatorial Administration of CD1c (BDCA-1)(+) Myeloid Dendritic Cells Plus Ipilimumab and Avelumab in Combination with Intravenous Low-Dose Nivolumab in Patients with Advanced Solid Tumors: A Phase IB Clinical Trial

Intratumoral (IT) myeloid dendritic cells (myDCs) play a pivotal role in re-licensing antitumor cytotoxic T lymphocytes. IT injection of the IgG(1) monoclonal antibodies ipilimumab and avelumab may induce antibody-dependent cellular cytotoxicity, thereby enhancing the release of tumor antigens that...

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Autores principales: Schwarze, Julia Katharina, Awada, Gil, Cras, Louise, Tijtgat, Jens, Forsyth, Ramses, Dufait, Inès, Tuyaerts, Sandra, Van Riet, Ivan, Neyns, Bart
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712037/
https://www.ncbi.nlm.nih.gov/pubmed/33182610
http://dx.doi.org/10.3390/vaccines8040670
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author Schwarze, Julia Katharina
Awada, Gil
Cras, Louise
Tijtgat, Jens
Forsyth, Ramses
Dufait, Inès
Tuyaerts, Sandra
Van Riet, Ivan
Neyns, Bart
author_facet Schwarze, Julia Katharina
Awada, Gil
Cras, Louise
Tijtgat, Jens
Forsyth, Ramses
Dufait, Inès
Tuyaerts, Sandra
Van Riet, Ivan
Neyns, Bart
author_sort Schwarze, Julia Katharina
collection PubMed
description Intratumoral (IT) myeloid dendritic cells (myDCs) play a pivotal role in re-licensing antitumor cytotoxic T lymphocytes. IT injection of the IgG(1) monoclonal antibodies ipilimumab and avelumab may induce antibody-dependent cellular cytotoxicity, thereby enhancing the release of tumor antigens that can be captured and processed by CD1c (BDCA-1)(+) myDCs. Patients with advanced solid tumors after standard care were eligible for IT injections of ≥1 lesion with ipilimumab (10 mg) and avelumab (40 mg) and intravenous (IV) nivolumab (10 mg) on day 1, followed by IT injection of autologous CD1c (BDCA-1)(+) myDCs on day 2. IT/IV administration of ipilimumab, avelumab, and nivolumab was repeated bi-weekly. Primary objectives were safety and feasibility. Nine patients were treated with a median of 21 × 10(6) CD1c (BDCA-1)(+) myDCs, and a median of 4 IT/IV administrations of ipilimumab, avelumab, and nivolumab. The treatment was safe with mainly injection-site reactions, but also immune-related pneumonitis (n = 2), colitis (n = 1), and bullous pemphigoid (n = 1). The best response was a durable partial response in a patient with stage IV melanoma who previously progressed on checkpoint inhibitors. Our combinatorial therapeutic approach, including IT injection of CD1c (BDCA-1)(+) myDCs, is feasible and safe, and it resulted in encouraging signs of antitumor activity in patients with advanced solid tumors.
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spelling pubmed-77120372020-12-04 Intratumoral Combinatorial Administration of CD1c (BDCA-1)(+) Myeloid Dendritic Cells Plus Ipilimumab and Avelumab in Combination with Intravenous Low-Dose Nivolumab in Patients with Advanced Solid Tumors: A Phase IB Clinical Trial Schwarze, Julia Katharina Awada, Gil Cras, Louise Tijtgat, Jens Forsyth, Ramses Dufait, Inès Tuyaerts, Sandra Van Riet, Ivan Neyns, Bart Vaccines (Basel) Article Intratumoral (IT) myeloid dendritic cells (myDCs) play a pivotal role in re-licensing antitumor cytotoxic T lymphocytes. IT injection of the IgG(1) monoclonal antibodies ipilimumab and avelumab may induce antibody-dependent cellular cytotoxicity, thereby enhancing the release of tumor antigens that can be captured and processed by CD1c (BDCA-1)(+) myDCs. Patients with advanced solid tumors after standard care were eligible for IT injections of ≥1 lesion with ipilimumab (10 mg) and avelumab (40 mg) and intravenous (IV) nivolumab (10 mg) on day 1, followed by IT injection of autologous CD1c (BDCA-1)(+) myDCs on day 2. IT/IV administration of ipilimumab, avelumab, and nivolumab was repeated bi-weekly. Primary objectives were safety and feasibility. Nine patients were treated with a median of 21 × 10(6) CD1c (BDCA-1)(+) myDCs, and a median of 4 IT/IV administrations of ipilimumab, avelumab, and nivolumab. The treatment was safe with mainly injection-site reactions, but also immune-related pneumonitis (n = 2), colitis (n = 1), and bullous pemphigoid (n = 1). The best response was a durable partial response in a patient with stage IV melanoma who previously progressed on checkpoint inhibitors. Our combinatorial therapeutic approach, including IT injection of CD1c (BDCA-1)(+) myDCs, is feasible and safe, and it resulted in encouraging signs of antitumor activity in patients with advanced solid tumors. MDPI 2020-11-10 /pmc/articles/PMC7712037/ /pubmed/33182610 http://dx.doi.org/10.3390/vaccines8040670 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schwarze, Julia Katharina
Awada, Gil
Cras, Louise
Tijtgat, Jens
Forsyth, Ramses
Dufait, Inès
Tuyaerts, Sandra
Van Riet, Ivan
Neyns, Bart
Intratumoral Combinatorial Administration of CD1c (BDCA-1)(+) Myeloid Dendritic Cells Plus Ipilimumab and Avelumab in Combination with Intravenous Low-Dose Nivolumab in Patients with Advanced Solid Tumors: A Phase IB Clinical Trial
title Intratumoral Combinatorial Administration of CD1c (BDCA-1)(+) Myeloid Dendritic Cells Plus Ipilimumab and Avelumab in Combination with Intravenous Low-Dose Nivolumab in Patients with Advanced Solid Tumors: A Phase IB Clinical Trial
title_full Intratumoral Combinatorial Administration of CD1c (BDCA-1)(+) Myeloid Dendritic Cells Plus Ipilimumab and Avelumab in Combination with Intravenous Low-Dose Nivolumab in Patients with Advanced Solid Tumors: A Phase IB Clinical Trial
title_fullStr Intratumoral Combinatorial Administration of CD1c (BDCA-1)(+) Myeloid Dendritic Cells Plus Ipilimumab and Avelumab in Combination with Intravenous Low-Dose Nivolumab in Patients with Advanced Solid Tumors: A Phase IB Clinical Trial
title_full_unstemmed Intratumoral Combinatorial Administration of CD1c (BDCA-1)(+) Myeloid Dendritic Cells Plus Ipilimumab and Avelumab in Combination with Intravenous Low-Dose Nivolumab in Patients with Advanced Solid Tumors: A Phase IB Clinical Trial
title_short Intratumoral Combinatorial Administration of CD1c (BDCA-1)(+) Myeloid Dendritic Cells Plus Ipilimumab and Avelumab in Combination with Intravenous Low-Dose Nivolumab in Patients with Advanced Solid Tumors: A Phase IB Clinical Trial
title_sort intratumoral combinatorial administration of cd1c (bdca-1)(+) myeloid dendritic cells plus ipilimumab and avelumab in combination with intravenous low-dose nivolumab in patients with advanced solid tumors: a phase ib clinical trial
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712037/
https://www.ncbi.nlm.nih.gov/pubmed/33182610
http://dx.doi.org/10.3390/vaccines8040670
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