The Dual Cell Cycle Kinase Inhibitor JNJ-7706621 Reverses Resistance to CD37-Targeted Radioimmunotherapy in Activated B Cell Like Diffuse Large B Cell Lymphoma Cell Lines

The CD37 targeting radioimmunoconjugate (177)Lu-lilotomab satetraxetan (Betalutin) is currently being evaluated in a clinical phase 2b trial for patients with follicular lymphoma (FL) and in a phase 1 trial for patients with diffuse large B-cell lymphoma (DLBCL). Herein we have investigated the effe...

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Autores principales: Rødland, Gro Elise, Melhus, Katrine, Generalov, Roman, Gilani, Sania, Bertoni, Francesco, Dahle, Jostein, Syljuåsen, Randi G., Patzke, Sebastian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Oncology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897291/
https://www.ncbi.nlm.nih.gov/pubmed/31850205
http://dx.doi.org/10.3389/fonc.2019.01301
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author Rødland, Gro Elise
Melhus, Katrine
Generalov, Roman
Gilani, Sania
Bertoni, Francesco
Dahle, Jostein
Syljuåsen, Randi G.
Patzke, Sebastian
author_facet Rødland, Gro Elise
Melhus, Katrine
Generalov, Roman
Gilani, Sania
Bertoni, Francesco
Dahle, Jostein
Syljuåsen, Randi G.
Patzke, Sebastian
author_sort Rødland, Gro Elise
collection PubMed
description The CD37 targeting radioimmunoconjugate (177)Lu-lilotomab satetraxetan (Betalutin) is currently being evaluated in a clinical phase 2b trial for patients with follicular lymphoma (FL) and in a phase 1 trial for patients with diffuse large B-cell lymphoma (DLBCL). Herein we have investigated the effect of (177)Lu-lilotomab satetraxetan in seven activated B-cell like (ABC) DLBCL cell lines. Although the radioimmunoconjugate showed anti-tumor activity, primary resistance was observed in a subset of cell lines. Thus, we set out to identify drugs able to overcome the resistance to (177)Lu-lilotomab satetraxetan in two resistant ABC-DLBCL cell lines. We performed a viability-based screen combining (177)Lu-lilotomab satetraxetan with the 384-compound Cambridge Cancer Compound Library. Drug combinations were scored using Bliss and Chou-Talalay algorithms. We identified and characterized the dual-specific CDK1/2 and AURA/B kinase inhibitor JNJ-7706621 as compound able to revert the resistance to RIT, alongside topoisomerase and histone deacetylases (HDAC) inhibitors.
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spelling pubmed-68972912019-12-17 The Dual Cell Cycle Kinase Inhibitor JNJ-7706621 Reverses Resistance to CD37-Targeted Radioimmunotherapy in Activated B Cell Like Diffuse Large B Cell Lymphoma Cell Lines Rødland, Gro Elise Melhus, Katrine Generalov, Roman Gilani, Sania Bertoni, Francesco Dahle, Jostein Syljuåsen, Randi G. Patzke, Sebastian Front Oncol Oncology The CD37 targeting radioimmunoconjugate (177)Lu-lilotomab satetraxetan (Betalutin) is currently being evaluated in a clinical phase 2b trial for patients with follicular lymphoma (FL) and in a phase 1 trial for patients with diffuse large B-cell lymphoma (DLBCL). Herein we have investigated the effect of (177)Lu-lilotomab satetraxetan in seven activated B-cell like (ABC) DLBCL cell lines. Although the radioimmunoconjugate showed anti-tumor activity, primary resistance was observed in a subset of cell lines. Thus, we set out to identify drugs able to overcome the resistance to (177)Lu-lilotomab satetraxetan in two resistant ABC-DLBCL cell lines. We performed a viability-based screen combining (177)Lu-lilotomab satetraxetan with the 384-compound Cambridge Cancer Compound Library. Drug combinations were scored using Bliss and Chou-Talalay algorithms. We identified and characterized the dual-specific CDK1/2 and AURA/B kinase inhibitor JNJ-7706621 as compound able to revert the resistance to RIT, alongside topoisomerase and histone deacetylases (HDAC) inhibitors. Frontiers Media S.A. 2019-11-29 /pmc/articles/PMC6897291/ /pubmed/31850205 http://dx.doi.org/10.3389/fonc.2019.01301 Text en Copyright © 2019 Rødland, Melhus, Generalov, Gilani, Bertoni, Dahle, Syljuåsen and Patzke. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Rødland, Gro Elise
Melhus, Katrine
Generalov, Roman
Gilani, Sania
Bertoni, Francesco
Dahle, Jostein
Syljuåsen, Randi G.
Patzke, Sebastian
The Dual Cell Cycle Kinase Inhibitor JNJ-7706621 Reverses Resistance to CD37-Targeted Radioimmunotherapy in Activated B Cell Like Diffuse Large B Cell Lymphoma Cell Lines
title The Dual Cell Cycle Kinase Inhibitor JNJ-7706621 Reverses Resistance to CD37-Targeted Radioimmunotherapy in Activated B Cell Like Diffuse Large B Cell Lymphoma Cell Lines
title_full The Dual Cell Cycle Kinase Inhibitor JNJ-7706621 Reverses Resistance to CD37-Targeted Radioimmunotherapy in Activated B Cell Like Diffuse Large B Cell Lymphoma Cell Lines
title_fullStr The Dual Cell Cycle Kinase Inhibitor JNJ-7706621 Reverses Resistance to CD37-Targeted Radioimmunotherapy in Activated B Cell Like Diffuse Large B Cell Lymphoma Cell Lines
title_full_unstemmed The Dual Cell Cycle Kinase Inhibitor JNJ-7706621 Reverses Resistance to CD37-Targeted Radioimmunotherapy in Activated B Cell Like Diffuse Large B Cell Lymphoma Cell Lines
title_short The Dual Cell Cycle Kinase Inhibitor JNJ-7706621 Reverses Resistance to CD37-Targeted Radioimmunotherapy in Activated B Cell Like Diffuse Large B Cell Lymphoma Cell Lines
title_sort dual cell cycle kinase inhibitor jnj-7706621 reverses resistance to cd37-targeted radioimmunotherapy in activated b cell like diffuse large b cell lymphoma cell lines
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897291/
https://www.ncbi.nlm.nih.gov/pubmed/31850205
http://dx.doi.org/10.3389/fonc.2019.01301
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