Nanoencapsulated rituximab mediates superior cellular immunity against metastatic B-cell lymphoma in a complement competent humanized mouse model.
Nanoencapsulated rituximab mediates superior cellular immunity against metastatic B-cell lymphoma in a complement competent humanized mouse model.
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纳米囊化的利妥昔单抗在补体有效的人源性小鼠模型中介导了针对转移性B细胞淋巴瘤的上等细胞免疫。
DOI：
10.1136/jitc-2020-001524
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发表时间：
2021-03
影响因子：
10.9
通讯作者：
Kamata M
中科院分区：
文献类型：
--
作者：
Wen J;Wang L;Ren J;Kranz E;Chen S;Wu D;Kanazawa T;Chen I;Lu Y;Kamata M
尽管单克隆抗体（mab）在癌症治疗中的应用众多，但用于测试新单克隆抗体治疗效果的动物模型是有限的。点头。Cg-Prkdcscid Il2rgtm1Wjl/SzJ （NSG）小鼠是最高度免疫缺陷的菌株之一，被普遍用作检测癌症靶向单克隆抗体的模型。然而，由于缺乏免疫细胞和Hc基因突变，该菌株缺乏充分支持抗体介导的效应功能所必需的几个因素，包括抗体依赖性细胞毒性、抗体依赖性细胞吞噬和补体依赖性细胞毒性（CDC），这是功能性补体系统所必需的。我们使用一种新的NSG菌株NOD开发了一种人源化小鼠模型。Cg−Hc1Prkdcscid Il2rgtm1Wjl/SzJ (NSG−Hc1)，包含Hc基因的纠正突变，除了人源化赋予的其他机制外，还支持CDC。利用该模型，我们重新评估了纳米包膜利妥昔单抗在人伯基特淋巴瘤细胞系2F7-BR44异种移植后的抗癌效果。正如预期的那样，与亲代NSG菌株相比，异种移植的人源化NSG−Hc1小鼠对原生利妥昔单抗的清除能力更高。纳米封装的利妥昔单抗结合CXCL13作为淋巴瘤靶向配体，进一步增强了NSG−Hc1小鼠的抗淋巴瘤活性，更重要的是，介导了抗淋巴瘤细胞反应。这些结果表明，NSG−Hc1小鼠可以作为研究肿瘤靶向治疗和了解抗肿瘤细胞免疫反应诱导机制的可行模型。
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. 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. 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. 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.
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影响因子：
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作者：
Haihua C;Wei W;Kun H;Yuanli L;Fei L
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影响因子：
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DOI：
10.1084/jem.20050915
发表时间：
2005-12-19
期刊：
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影响因子：
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影响因子：
20.3
作者：
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作者：
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