GA101 P329GLALA, a variant of obinutuzumab with abolished ADCC, ADCP and CDC function but retained cell death induction, is as efficient as rituximab in B-cell depletion and antitumor activity.
作者信息
Herter Sylvia, Herting Frank, Muth Gunter, van Puijenbroek Erwin, Schlothauer Tilman, Ferrara Claudia, Brady Kevin, Lang Sabine, Bacac Marina, Mössner Ekkehard, Umana Pablo, Klein Christian
机构信息
Roche Pharmaceutical Research & Early Development, 1Roche Innovation Center Zurich, Switzerland.
Roche Innovation Center Munich, Germany.
出版信息
Haematologica. 2018 Feb;103(2):e78-e81. doi: 10.3324/haematol.2017.178996. Epub 2017 Oct 27.
Abstract
摘要
相似文献
1
GA101 P329GLALA, a variant of obinutuzumab with abolished ADCC, ADCP and CDC function but retained cell death induction, is as efficient as rituximab in B-cell depletion and antitumor activity.GA101 P329GLALA是奥滨尤妥珠单抗的一种变体，其抗体依赖的细胞介导的细胞毒性（ADCC）、抗体依赖的细胞吞噬作用（ADCP）和补体依赖的细胞毒性（CDC）功能被消除，但保留了诱导细胞死亡的能力，在B细胞清除和抗肿瘤活性方面与利妥昔单抗一样有效。
Haematologica. 2018 Feb;103(2):e78-e81. doi: 10.3324/haematol.2017.178996. Epub 2017 Oct 27.
2
Antitumour activity of the glycoengineered type II anti-CD20 antibody obinutuzumab (GA101) in combination with the MDM2-selective antagonist idasanutlin (RG7388).糖基工程化II型抗CD20抗体奥滨尤妥珠单抗（GA101）与MDM2选择性拮抗剂idasanutlin（RG7388）联合应用的抗肿瘤活性。
Eur J Haematol. 2016 Nov;97(5):461-470. doi: 10.1111/ejh.12756. Epub 2016 Apr 18.
3
Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models.GA101（奥滨尤妥珠单抗，一种 II 型 CD20 抗体）与利妥昔单抗和奥法木单抗的体外及异种移植模型中的临床前活性比较。
Mol Cancer Ther. 2013 Oct;12(10):2031-42. doi: 10.1158/1535-7163.MCT-12-1182. Epub 2013 Jul 19.
4
Obinutuzumab (GA101) is highly effective against chronic lymphocytic leukemia cells in ex vivo B-cell depletion irrespective of high-risk prognostic markers.奥滨尤妥珠单抗（GA101）在体外B细胞清除中对慢性淋巴细胞白血病细胞具有高度有效性，无论其高危预后标志物如何。
Blood Cancer J. 2015 Nov 13;5(11):e367. doi: 10.1038/bcj.2015.93.
5
Follicular lymphoma: in vitro effects of combining lymphokine-activated killer (LAK) cell-induced cytotoxicity and rituximab- and obinutuzumab-dependent cellular cytotoxicity (ADCC) activity.滤泡性淋巴瘤：联合淋巴因子激活的杀伤（LAK）细胞诱导的细胞毒性与利妥昔单抗和奥滨尤妥珠单抗依赖性细胞毒性（ADCC）活性的体外效应
Immunol Res. 2016 Apr;64(2):548-57. doi: 10.1007/s12026-015-8747-9.
6
Obinutuzumab (GA101) compared to rituximab significantly enhances cell death and antibody-dependent cytotoxicity and improves overall survival against CD20(+) rituximab-sensitive/-resistant Burkitt lymphoma (BL) and precursor B-acute lymphoblastic leukaemia (pre-B-ALL): potential targeted therapy in patients with poor risk CD20(+) BL and pre-B-ALL.奥滨尤妥珠单抗（GA101）与利妥昔单抗相比，能显著增强细胞死亡和抗体依赖性细胞毒性，并改善针对 CD20（+）利妥昔单抗敏感/耐药伯基特淋巴瘤（BL）和前体 B 急性淋巴细胞白血病（pre-B-ALL）的总体生存率：对高危 CD20（+）BL 和 pre-B-ALL 患者具有潜在的靶向治疗作用。
Br J Haematol. 2015 Dec;171(5):763-75. doi: 10.1111/bjh.13764. Epub 2015 Oct 16.
7
Comparison of the in vitro effects of the anti-CD20 antibodies rituximab and GA101 on chronic lymphocytic leukaemia cells.比较抗 CD20 抗体利妥昔单抗和 GA101 对慢性淋巴细胞白血病细胞的体外作用。
Br J Haematol. 2011 Feb;152(3):295-306. doi: 10.1111/j.1365-2141.2010.08428.x. Epub 2010 Dec 13.
8
KIR/HLA interactions negatively affect rituximab- but not GA101 (obinutuzumab)-induced antibody-dependent cellular cytotoxicity.KIR/HLA 相互作用对利妥昔单抗而非 GA101（奥滨尤妥珠单抗）诱导的抗体依赖性细胞细胞毒性有负面影响。
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Obinutuzumab (GA101) for the treatment of chronic lymphocytic leukemia and other B-cell non-hodgkin's lymphomas: a glycoengineered type II CD20 antibody.奥滨尤妥珠单抗（GA101）治疗慢性淋巴细胞白血病和其他 B 细胞非霍奇金淋巴瘤：一种糖基化工程化的 II 型 CD20 抗体。
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Intravital imaging reveals improved Kupffer cell-mediated phagocytosis as a mode of action of glycoengineered anti-CD20 antibodies.活体成像显示，糖基化抗 CD20 抗体改善了枯否细胞介导的吞噬作用，这是其作用机制之一。
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本文引用的文献
1
Obinutuzumab for the First-Line Treatment of Follicular Lymphoma.奥滨尤妥珠单抗用于滤泡性淋巴瘤的一线治疗。
N Engl J Med. 2017 Oct 5;377(14):1331-1344. doi: 10.1056/NEJMoa1614598.
2
Novel human IgG1 and IgG4 Fc-engineered antibodies with completely abolished immune effector functions.具有完全消除的免疫效应功能的新型人IgG1和IgG4 Fc工程抗体。
Protein Eng Des Sel. 2016 Oct;29(10):457-466. doi: 10.1093/protein/gzw040. Epub 2016 Aug 29.
3
Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial.奥滨尤妥珠单抗联合苯达莫司汀对比苯达莫司汀单药治疗利妥昔单抗难治性惰性非霍奇金淋巴瘤（GADOLIN）：一项随机、对照、开放标签、多中心、3 期临床试验。
Lancet Oncol. 2016 Aug;17(8):1081-1093. doi: 10.1016/S1470-2045(16)30097-3. Epub 2016 Jun 23.
4
Obinutuzumab (GA101) is highly effective against chronic lymphocytic leukemia cells in ex vivo B-cell depletion irrespective of high-risk prognostic markers.奥滨尤妥珠单抗（GA101）在体外B细胞清除中对慢性淋巴细胞白血病细胞具有高度有效性，无论其高危预后标志物如何。
Blood Cancer J. 2015 Nov 13;5(11):e367. doi: 10.1038/bcj.2015.93.
5
Development and Characterization of Monoclonal Antibodies Specific for Mouse and Human Fcγ Receptors.针对小鼠和人Fcγ受体的单克隆抗体的开发与特性分析
J Immunol. 2015 Dec 1;195(11):5503-16. doi: 10.4049/jimmunol.1402988. Epub 2015 Oct 28.
6
Cytokine release in patients with CLL treated with obinutuzumab and possible relationship with infusion-related reactions.接受奥滨尤妥珠单抗治疗的慢性淋巴细胞白血病患者的细胞因子释放及其与输注相关反应的可能关系。
Blood. 2015 Dec 10;126(24):2646-9. doi: 10.1182/blood-2015-09-670802. Epub 2015 Oct 7.
7
Obinutuzumab in hematologic malignancies: lessons learned to date.奥滨尤妥珠单抗在血液恶性肿瘤中的应用：迄今为止的经验教训。
Cancer Treat Rev. 2015 Nov;41(9):784-92. doi: 10.1016/j.ctrv.2015.07.003. Epub 2015 Jul 14.
8
Obinutuzumab (GA101) for the treatment of chronic lymphocytic leukemia and other B-cell non-hodgkin's lymphomas: a glycoengineered type II CD20 antibody.奥滨尤妥珠单抗（GA101）治疗慢性淋巴细胞白血病和其他 B 细胞非霍奇金淋巴瘤：一种糖基化工程化的 II 型 CD20 抗体。
Oncol Res Treat. 2015;38(4):185-92. doi: 10.1159/000381524. Epub 2015 Mar 31.
9
Antigenic modulation limits the effector cell mechanisms employed by type I anti-CD20 monoclonal antibodies.抗原调节限制了 I 型抗 CD20 单克隆抗体所采用的效应细胞机制。
Blood. 2015 Mar 19;125(12):1901-9. doi: 10.1182/blood-2014-07-588376. Epub 2015 Jan 28.
10
U.S. Food and drug administration approval: obinutuzumab in combination with chlorambucil for the treatment of previously untreated chronic lymphocytic leukemia.美国食品药品监督管理局批准：奥滨尤妥珠单抗联合苯丁酸氮芥治疗未经治疗的慢性淋巴细胞白血病。
Clin Cancer Res. 2014 Aug 1;20(15):3902-7. doi: 10.1158/1078-0432.CCR-14-0516. Epub 2014 May 13.
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