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Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab (GA101) in combination with chemotherapy in xenograft models of human lymphoma

Obinutuzumab (GA101) is a novel glycoengineered type II CD20 antibody in development for non-Hodgkin lymphoma. We compared the anti-tumor activity of obinutuzumab and rituximab in preclinical studies using subcutaneous Z138 and WSU-DLCL2 xenograft mouse models. Obinutuzumab and rituximab were assess...

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Autores principales: Herting, Frank, Friess, Thomas, Bader, Sabine, Muth, Gunter, Hölzlwimmer, Gabriele, Rieder, Natascha, Umana, Pablo, Klein, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Informa Healthcare 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196549/
https://www.ncbi.nlm.nih.gov/pubmed/24304419
http://dx.doi.org/10.3109/10428194.2013.856008
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author Herting, Frank
Friess, Thomas
Bader, Sabine
Muth, Gunter
Hölzlwimmer, Gabriele
Rieder, Natascha
Umana, Pablo
Klein, Christian
author_facet Herting, Frank
Friess, Thomas
Bader, Sabine
Muth, Gunter
Hölzlwimmer, Gabriele
Rieder, Natascha
Umana, Pablo
Klein, Christian
author_sort Herting, Frank
collection PubMed
description Obinutuzumab (GA101) is a novel glycoengineered type II CD20 antibody in development for non-Hodgkin lymphoma. We compared the anti-tumor activity of obinutuzumab and rituximab in preclinical studies using subcutaneous Z138 and WSU-DLCL2 xenograft mouse models. Obinutuzumab and rituximab were assessed alone and in combination with bendamustine, fludarabine, chlorambucil, doxorubicin and cyclophosphamide/vincristine. Owing to strong single-agent efficacy in these models, suboptimal doses of obinutuzumab were applied to demonstrate a combination effect. Obinutuzumab plus bendamustine achieved superior tumor growth inhibition versus rituximab plus bendamustine and showed a statistically significant effect versus the respective single treatments. Combinations of obinutuzumab with fludarabine, chlorambucil or cyclophosphamide/vincristine demonstrated significantly superior activity to rituximab-based treatment. Obinutuzumab monotherapy was at least as effective as rituximab plus chemotherapy in vivo, and obinutuzumab plus chemotherapy was superior to the respective monotherapies. These data support further clinical investigation of obinutuzumab plus chemotherapy.
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spelling pubmed-41965492014-10-27 Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab (GA101) in combination with chemotherapy in xenograft models of human lymphoma Herting, Frank Friess, Thomas Bader, Sabine Muth, Gunter Hölzlwimmer, Gabriele Rieder, Natascha Umana, Pablo Klein, Christian Leuk Lymphoma Original Article: Research Obinutuzumab (GA101) is a novel glycoengineered type II CD20 antibody in development for non-Hodgkin lymphoma. We compared the anti-tumor activity of obinutuzumab and rituximab in preclinical studies using subcutaneous Z138 and WSU-DLCL2 xenograft mouse models. Obinutuzumab and rituximab were assessed alone and in combination with bendamustine, fludarabine, chlorambucil, doxorubicin and cyclophosphamide/vincristine. Owing to strong single-agent efficacy in these models, suboptimal doses of obinutuzumab were applied to demonstrate a combination effect. Obinutuzumab plus bendamustine achieved superior tumor growth inhibition versus rituximab plus bendamustine and showed a statistically significant effect versus the respective single treatments. Combinations of obinutuzumab with fludarabine, chlorambucil or cyclophosphamide/vincristine demonstrated significantly superior activity to rituximab-based treatment. Obinutuzumab monotherapy was at least as effective as rituximab plus chemotherapy in vivo, and obinutuzumab plus chemotherapy was superior to the respective monotherapies. These data support further clinical investigation of obinutuzumab plus chemotherapy. Informa Healthcare 2014-09 2013-02-04 /pmc/articles/PMC4196549/ /pubmed/24304419 http://dx.doi.org/10.3109/10428194.2013.856008 Text en © 2014 Informa UK, Ltd. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the CC-BY-NC-ND 3.0 License which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is credited.
spellingShingle Original Article: Research
Herting, Frank
Friess, Thomas
Bader, Sabine
Muth, Gunter
Hölzlwimmer, Gabriele
Rieder, Natascha
Umana, Pablo
Klein, Christian
Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab (GA101) in combination with chemotherapy in xenograft models of human lymphoma
title Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab (GA101) in combination with chemotherapy in xenograft models of human lymphoma
title_full Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab (GA101) in combination with chemotherapy in xenograft models of human lymphoma
title_fullStr Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab (GA101) in combination with chemotherapy in xenograft models of human lymphoma
title_full_unstemmed Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab (GA101) in combination with chemotherapy in xenograft models of human lymphoma
title_short Enhanced anti-tumor activity of the glycoengineered type II CD20 antibody obinutuzumab (GA101) in combination with chemotherapy in xenograft models of human lymphoma
title_sort enhanced anti-tumor activity of the glycoengineered type ii cd20 antibody obinutuzumab (ga101) in combination with chemotherapy in xenograft models of human lymphoma
topic Original Article: Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196549/
https://www.ncbi.nlm.nih.gov/pubmed/24304419
http://dx.doi.org/10.3109/10428194.2013.856008
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