Nanoencapsulated rituximab mediates superior cellular immunity against metastatic B-cell lymphoma in a complement competent humanized mouse model

Background Despite the numerous applications of monoclonal antibodies (mAbs) in cancer therapeutics, animal models available to test the therapeutic efficacy of new mAbs are limited. NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice are one of the most highly immunodeficient strains and are universally us...

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Autores principales:	Lan Wang, Jing Wen, Jie Ren, Emiko Kranz, Shilin Chen, Toshio Kanazawa, Irvin Chen, Yunfeng Lu, Masakazu Kamata
Formato:	article
Lenguaje:	EN
Publicado:	BMJ Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/e913defc66ea41f4a4af89a8552834da
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spelling	oai:doaj.org-article:e913defc66ea41f4a4af89a8552834da2021-11-15T23:30:04ZNanoencapsulated rituximab mediates superior cellular immunity against metastatic B-cell lymphoma in a complement competent humanized mouse model10.1136/jitc-2020-0015242051-1426https://doaj.org/article/e913defc66ea41f4a4af89a8552834da2021-02-01T00:00:00Zhttps://jitc.bmj.com/content/9/2/e001524.fullhttps://doaj.org/toc/2051-1426Background Despite the numerous applications of monoclonal antibodies (mAbs) in cancer therapeutics, animal models available to test the therapeutic efficacy of new mAbs are limited. NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice are one of the most highly immunodeficient strains and are universally used as a model for testing cancer-targeting mAbs. However, this strain lacks several factors necessary to fully support antibody-mediated effector functions—including antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity (CDC)—due to the absence of immune cells as well as a mutation in the Hc gene, which is needed for a functional complement system.Methods We have developed a humanized mouse model using a novel NSG strain, NOD.Cg−Hc1Prkdcscid Il2rgtm1Wjl/SzJ (NSG−Hc1), which contains the corrected mutation in the Hc gene to support CDC in addition to other mechanisms endowed by humanization. With this model, we reevaluated the anticancer efficacies of nanoencapsulated rituximab after xenograft of the human Burkitt lymphoma cell line 2F7-BR44.Results As expected, xenografted humanized NSG−Hc1 mice supported superior lymphoma clearance of native rituximab compared with the parental NSG strain. Nanoencapsulated rituximab with CXCL13 conjugation as a targeting ligand for lymphomas further enhanced antilymphoma activity in NSG−Hc1 mice and, more importantly, mediated antilymphoma cellular responses.Conclusions These results indicate that NSG−Hc1 mice can serve as a feasible model for both studying antitumor treatment using cancer targeting as well as understanding induction mechanisms of antitumor cellular immune response.Lan WangJing WenJie RenEmiko KranzShilin ChenToshio KanazawaIrvin ChenYunfeng LuMasakazu KamataBMJ Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal for ImmunoTherapy of Cancer, Vol 9, Iss 2 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Lan Wang Jing Wen Jie Ren Emiko Kranz Shilin Chen Toshio Kanazawa Irvin Chen Yunfeng Lu Masakazu Kamata Nanoencapsulated rituximab mediates superior cellular immunity against metastatic B-cell lymphoma in a complement competent humanized mouse model
description	Background Despite the numerous applications of monoclonal antibodies (mAbs) in cancer therapeutics, animal models available to test the therapeutic efficacy of new mAbs are limited. NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice are one of the most highly immunodeficient strains and are universally used as a model for testing cancer-targeting mAbs. However, this strain lacks several factors necessary to fully support antibody-mediated effector functions—including antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity (CDC)—due to the absence of immune cells as well as a mutation in the Hc gene, which is needed for a functional complement system.Methods We have developed a humanized mouse model using a novel NSG strain, NOD.Cg−Hc1Prkdcscid Il2rgtm1Wjl/SzJ (NSG−Hc1), which contains the corrected mutation in the Hc gene to support CDC in addition to other mechanisms endowed by humanization. With this model, we reevaluated the anticancer efficacies of nanoencapsulated rituximab after xenograft of the human Burkitt lymphoma cell line 2F7-BR44.Results As expected, xenografted humanized NSG−Hc1 mice supported superior lymphoma clearance of native rituximab compared with the parental NSG strain. Nanoencapsulated rituximab with CXCL13 conjugation as a targeting ligand for lymphomas further enhanced antilymphoma activity in NSG−Hc1 mice and, more importantly, mediated antilymphoma cellular responses.Conclusions These results indicate that NSG−Hc1 mice can serve as a feasible model for both studying antitumor treatment using cancer targeting as well as understanding induction mechanisms of antitumor cellular immune response.
format	article
author	Lan Wang Jing Wen Jie Ren Emiko Kranz Shilin Chen Toshio Kanazawa Irvin Chen Yunfeng Lu Masakazu Kamata
author_facet	Lan Wang Jing Wen Jie Ren Emiko Kranz Shilin Chen Toshio Kanazawa Irvin Chen Yunfeng Lu Masakazu Kamata
author_sort	Lan Wang
title	Nanoencapsulated rituximab mediates superior cellular immunity against metastatic B-cell lymphoma in a complement competent humanized mouse model
title_short	Nanoencapsulated rituximab mediates superior cellular immunity against metastatic B-cell lymphoma in a complement competent humanized mouse model
title_full	Nanoencapsulated rituximab mediates superior cellular immunity against metastatic B-cell lymphoma in a complement competent humanized mouse model
title_fullStr	Nanoencapsulated rituximab mediates superior cellular immunity against metastatic B-cell lymphoma in a complement competent humanized mouse model
title_full_unstemmed	Nanoencapsulated rituximab mediates superior cellular immunity against metastatic B-cell lymphoma in a complement competent humanized mouse model
title_sort	nanoencapsulated rituximab mediates superior cellular immunity against metastatic b-cell lymphoma in a complement competent humanized mouse model
publisher	BMJ Publishing Group
publishDate	2021
url	https://doaj.org/article/e913defc66ea41f4a4af89a8552834da
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Nanoencapsulated rituximab mediates superior cellular immunity against metastatic B-cell lymphoma in a complement competent humanized mouse model

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