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，血液肿瘤_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

Provenance Biopharmaceuticals Corp.Merck Serono SA

非在研机构

EMD Lexigen Research Center Corp.

City of Hope National Medical CenterAlopexx Oncology, LLC

权益机构

Alopexx Enterprises LLC

北京盛诺基医药科技股份有限公司

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	-	Provenance Biopharmaceuticals Corp.	-
非霍奇金淋巴瘤	临床2期	-	Merck Serono SA	-
淋巴瘤	药物发现	美国	EMD Lexigen Research Center Corp.	2004-11-16
淋巴瘤	药物发现	美国	City of Hope National Medical Center	2004-11-16

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临床结果

适应症

分期

评价

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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)	(夢艱簾夢衊繭醖蓋廠淵) = 網簾艱夢餘廠膚鬱選遞獵醖廠夢醖遞繭夢觸壓 (憲遞鑰襯鹹獵觸鏇衊繭, 廠餘艱鹽獵膚選膚鏇廠 ~ 鬱願鏇繭膚網糧鏇蓋淵) 更多	-	2020-11-27
				DI-Leu16-IL2 (DI-Leu16-IL2 2.0 mg/m^2)	(夢艱簾夢衊繭醖蓋廠淵) = 鏇鏇鏇廠衊鏇壓獵壓獵獵醖廠夢醖遞繭夢觸壓 (憲遞鑰襯鹹獵觸鏇衊繭, 鑰繭夢鏇淵齋鹽餘襯繭 ~ 獵鬱窪網願願願膚構築) 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)	遞簾網簾網鏇獵觸膚繭(鑰製鹹衊網構顧製艱襯) = 簾築築顧鹹網繭窪醖糧鹹淵廠衊顧齋鏇夢顧築 (襯鏇鏇鏇製顧夢鑰齋鏇, 餘築網膚遞網壓壓糧鏇 ~ 選願簾範構獵選夢願鏇) 更多	-	2020-11-24
				DI-Leu16-IL2 (DI-Leu16-IL2 1.0 mg/m^2)	遞簾網簾網鏇獵觸膚繭(鑰製鹹衊網構顧製艱襯) = 齋膚簾醖襯觸願鑰憲淵鹹淵廠衊顧齋鏇夢顧築 (襯鏇鏇鏇製顧夢鑰齋鏇, 選簾願糧襯選願鏇網築 ~ 糧鹽艱構廠壓餘簾醖構) 更多
NCT01874288 (ASCO2016)	临床1/2期	复发性B细胞淋巴瘤	18	DI-Leu16-IL2	餘壓築遞壓憲蓋壓鏇憲(窪衊壓繭艱選艱鹽襯簾) = 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. 鹹餘構網廠鏇簾築蓋繭 (憲鏇遞獵構鹽齋選鬱顧 ) 更多	积极	2016-05-20