DI-Leu16-IL2(DI-Leu16-IL2) - 药物靶点：CD20 x IL-2R_在研适应症：非霍奇金淋巴瘤，淋巴瘤_专利_临床

概要

基本信息

药物类型

抗体融合蛋白

别名

Anti-CD20 monoclonal antibody-interleukin-2 fusion protein、DI-Leu16-IL2 immunocytokine、de-immunized anti-CD20-IL-2 immunocytokine DI-Leu16-IL-2

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靶点

CD20 x IL-2R

作用方式

抑制剂、激动剂

作用机制

CD20抑制剂(B淋巴细胞抗原CD20抑制剂)、IL-2R激动剂(白细胞介素-2受体复合体激动剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

City of Hope National Medical CenterEMD Lexigen Research Center Corp.Merck Serono SA

+ [1]

非在研机构

Alopexx Oncology, LLC

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

Sequence Code 16279555VH

Sequence Code 14671992VL

关联

3

项与 DI-Leu16-IL2 相关的临床试验

NCT02151903

/ Terminated临床1/2期

An Open-Label Extension Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered in Patients With B-cell Non-Hodgkin Lymphoma (NHL)

This is an open-label extension study enrolling participants experiencing clinical benefit following 6 cycles of DI-Leu16-IL2 while enrolled in the Alopexx Oncology Dose-Escalation AO-101 study (NCT01874288). Participants will be permitted to continue to receive DI-Leu16-IL2 at the same dose, schedule, and route of administration they received during Study AO-101 (Main Study). Prior pre-treatment (for example, Rituximab) will continue as before.

开始日期2014-11-04

申办/合作机构

Alopexx Oncology, LLC

NCT01874288

/ Terminated临床1/2期

A Phase I/II Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered Subcutaneously in Patients With B-cell Non-Hodgkin Lymphoma (NHL)

This dose-escalation study is designed for determining the safety, tolerability, pharmacokinetics (PK), biological, and clinical activity of DI-Leu16-IL2 administered to participants with cluster of differentiation 20 (CD20) positive NHL that have failed standard rituximab-containing therapy.

开始日期2013-11-25

申办/合作机构

Alopexx Oncology, LLC

NCT00720135

/ Completed临床1期IIT

A Phase I Study of De-Immunized DI-Leu16-IL2 Immunocytokine in Patients With B-Cell Non-Hodgkin Lymphoma

RATIONALE: Biological therapies, such as fusion protein cytokine therapy, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving fusion protein cytokine therapy together with rituximab may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of fusion protein cytokine therapy when given after rituximab in treating patients with B-cell non-Hodgkin lymphoma.

开始日期2008-01-01

申办/合作机构

City of Hope National Medical Center

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100 项与 DI-Leu16-IL2 相关的临床结果

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100 项与 DI-Leu16-IL2 相关的转化医学

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100 项与 DI-Leu16-IL2 相关的专利（医药）

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1

项与 DI-Leu16-IL2 相关的文献（医药）

2005-05-15·Blood1区 · 医学

An anti-CD20–IL-2 immunocytokine is highly efficacious in a SCID mouse model of established human B lymphoma

1区 · 医学

Article

作者: Williams, Steven ; Carr, Frank ; Forman, Stephen ; Lan, Yan ; Raubitschek, Andrew ; Gillies, Stephen D. ; Lo, Kin-Ming

AbstractWe have engineered an anti-CD20–interleukin 2 (IL-2) immunocytokine (ICK) based on the Leu16 anti-CD20 antibody and have deimmunized both the variable (V) regions as well as the junction between the heavy (H) chain constant region and IL-2. Mutations were made to remove potential T-cell epitopes identified by in silico binding to major histocompatibility complex (MHC) class II molecules. The resulting immunocytokine, DI-Leu16-IL-2, retained full anti-CD20 activity as assessed by fluorescence-activated cell-sorting (FACS) analysis, and had enhanced antibody-dependent cellular cytotoxicity (ADCC) effector function relative to the DI-Leu16 antibody or control anti-CD20 antibody (rituximab). In a severe combined immunodeficient (SCID) mouse model of disseminated, residual lymphoma, anti-CD20–IL-2 immunocytokines based on Leu16 were far more effective at a dose of 0.25 mg/kg than anti-CD20 antibody given at 25/mg/kg, despite a shorter half-life of the ICK. Anti-CD20–IL-2 was also far more effective than a control ICK targeted to an antigen with greatly reduced expression on Daudi tumor cells, or various combinations of anti-CD20 antibodies and IL-2. Antitumor activity of DI-Leu16-IL-2 was shown to partially but not entirely depend on Fc receptor (R) binding, suggesting that ADCC and targeting of IL-2 both play roles in the mechanism of tumor clearance. Based on these animal models, DI-Leu16-IL-2 could offer therapeutic potential for patients with CD20 positive lymphoma. Clinical trials are currently under development.

100 项与 DI-Leu16-IL2 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
B细胞淋巴瘤	临床2期	美国	Alopexx Oncology, LLC	2013-11-25
非霍奇金淋巴瘤	临床2期	-	Merck Serono SA	-
非霍奇金淋巴瘤	临床2期	-	Provenance Biopharmaceuticals Corp.	-
淋巴瘤	临床前	美国	City of Hope National Medical Center	2004-11-16
淋巴瘤	临床前	美国	EMD Lexigen Research Center Corp.	2004-11-16

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02151903 (CTgov)	临床1/2期	B细胞淋巴瘤	5	DI-Leu16-IL2 (DI-Leu16-IL2 1.0 mg/m^2)	(膚醖製壓鑰遞積蓋憲衊) = 鏇鹽夢鑰遞網壓製積膚願顧築廠範鹽淵繭膚製 (願齋憲夢憲積鹽蓋膚積, 憲蓋積網積繭範窪鏇鏇 ~ 鏇選鏇醖積範廠鬱獵構) 更多	-	2020-11-27
				DI-Leu16-IL2 (DI-Leu16-IL2 2.0 mg/m^2)	(膚醖製壓鑰遞積蓋憲衊) = 築廠簾餘鏇顧鏇鏇網簾願顧築廠範鹽淵繭膚製 (願齋憲夢憲積鹽蓋膚積, 繭選艱構衊鬱簾築艱壓 ~ 鹹鏇顧夢繭觸鏇齋獵觸) 更多
NCT01874288 (DI-Leu16-IL2, CTgov)	临床1/2期	B细胞淋巴瘤	24	DI-Leu16-IL2 (DI-Leu16-IL2 0.5 mg/m^2)	網艱襯網遞襯鬱鏇遞鹹(築廠積壓簾艱網鏇衊願) = 艱糧襯觸壓膚構選衊鹹遞衊蓋網蓋繭觸構顧廠 (夢範鑰遞憲觸憲蓋積糧, 鏇淵顧艱衊齋範襯廠製 ~ 範衊遞繭鏇鬱構鏇窪壓) 更多	-	2020-11-24
				DI-Leu16-IL2 (DI-Leu16-IL2 1.0 mg/m^2)	網艱襯網遞襯鬱鏇遞鹹(築廠積壓簾艱網鏇衊願) = 構遞膚艱構齋顧窪積範遞衊蓋網蓋繭觸構顧廠 (夢範鑰遞憲觸憲蓋積糧, 齋蓋願衊夢窪夢願襯遞 ~ 鹹遞繭醖壓願壓鏇積選) 更多
NCT01874288 (ASCO2016)	临床1/2期	复发性B细胞淋巴瘤	18	DI-Leu16-IL2	夢顧憲醖獵選觸壓範觸(襯膚製憲鹹選艱淵鏇艱) = DLT occurred in 2 pts at 6 mg/m2 with delayed (8-10 days) grade 3 cytokine release syndrome, suggesting effector cell expansion as the cause. 壓夢簾築壓選鹹鏇積鏇 (廠窪範築夢齋糧糧淵艱 ) 更多	积极	2016-05-20