TALL-104(TALL-104) - _专利_临床

概要

基本信息

药物类型

T细胞疗法

别名

Human MHC non-restricted cytotoxic T-cell line - Galileo Research

+ [1]

靶点-

作用方式

刺激剂

作用机制

细胞死亡刺激剂、免疫细胞毒性、T淋巴细胞替代物

治疗领域

肿瘤免疫系统疾病内分泌与代谢疾病+ [3]

在研适应症-

非在研适应症

慢性期慢性髓性白血病白血病淋巴瘤+ [2]

原研机构

The Wistar Institute

在研机构-

非在研机构

Galileo Research Srl

The University of Texas MD Anderson Cancer Center

Abiogen Pharma SpA

权益机构-

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

登录后查看时间轴

关联

3

项与 TALL-104 相关的临床试验

EUCTR2013-001005-82-IT

/ Not yet recruiting临床2期

Phase II trial of intraperitoneal MHC unrestricted adoptive cell therapy with TALL-104 cells in patients with ovarian carcinoma with minimal or microscopic residual disease at second look laparotomy/laparoscopy

开始日期2015-05-05

申办/合作机构

Galileo Research Srl

NCT02210065

/ Completed临床2期IIT

The Pre-Emptive Use of Recipient-Derived Autologous Cytomegalovirus (CMV)-Specific Cytotoxic T Cells for Cytomegalovirus (CMV) Reactivation After Allogeneic Stem Cell Transplantation

The goal of this clinical research study is to learn if giving cytotoxic T lymphocytes (CTLs) can help control CMV when it reactivates (becomes active again) in patients who receive an allogeneic stem cell transplant. Researchers also want to learn about the safety of giving CTLs to patients who have had a stem cell transplant.

开始日期2015-03-03

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

NCT00415909

/ Terminated临床2期IIT

Phase II "Proof of Concept" Study of TALL-104 (MHC Non-Restricted Cytotoxic T-Cell Line) and Imatinib Mesylate (Gleevec) in Chronic Myelogenous Leukemia in Chronic Phase

Objectives:
To determine the response rate and duration of response with combination of TALL-104 cells and imatinib mesylate (IM) therapy in patients with chronic myelogenous leukemia in chronic phase, that have not achieved, or have lost, adequate response to IM.
To determine the toxicity of the combination of TALL-104 cells and IM therapy in this patient population.

开始日期2006-12-01

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

100 项与 TALL-104 相关的临床结果

登录后查看更多信息

100 项与 TALL-104 相关的转化医学

登录后查看更多信息

100 项与 TALL-104 相关的专利（医药）

登录后查看更多信息

18

项与 TALL-104 相关的文献（医药）

2010-12-01·BMC Neuroscience3区 · 医学

Multimodal investigations of trans-endothelial cell trafficking under condition of disrupted blood-brain barrier integrity

3区 · 医学

ArticleOA

作者: Minh T Nguyen ; Peter Rasmussen ; Thomas Masaryk ; Qingshan Teng ; Nicola Marchi ; Damir Janigro ; Silvia Trasciatti ; Nirav K Desai ; Linda Franic

AbstractBackgroundStem cells or immune cells targeting the central nervous system (CNS) bear significant promises for patients affected by CNS disorders. Brain or spinal cord delivery of therapeutic cells is limited by the blood-brain barrier (BBB) which remains one of the recognized rate-limiting steps. Osmotic BBB disruption (BBBD) has been shown to improve small molecule chemotherapy for brain tumors, but successful delivery of cells in conjunction with BBBD has never been reported.We have used a clinically relevant model (pig) of BBBD to attempt brain delivery of TALL-104, a human leukemic T cell line. TALL-104 cells are potent tumor killers and have demonstrated potential for systemic tumor therapy. The pig model used is analogous to the clinical BBBD procedure. Cells were injected in the carotid artery after labeling with the MRI T1 contrast agent GdHPDO3A. Contrast CT scans were used to quantify BBBD and MRI was used to detect Gd++-loaded cells in the brain. Transcranial Doppler was used to monitor cerebral blood flow. EEG recordings were used to detect seizures. Immunocytochemical detection (Cresyl Violet, anti-human CD8 for TALL-104, Evans Blue for BBB damage, GFAP and NEUN) was performed.ResultsAt the concentration used TALL-104 cells were tolerated. Incomplete BBBD did not allow cell entry into the brain. MRI scans at 24 and 48 hours post-injection allowed visualization of topographically segregated cells in the hemisphere that underwent successful BBBD. Perivascular location of TALL-104 was confirmed in the BBBD hemisphere by Cresyl violet and CD8 immunocytochemistry. No significant alteration in CBF or EEG activity was recorded during cell injections.ConclusionsOur data show that targeted CNS cell therapy requires blood-brain barrier disruption. MRI-detectable cytotoxic anti-neoplastic cells can be forced to transverse the BBB and accumulate in the perivascular space. The virtual absence of toxicity, the high anti-tumor activity of TALL-104, and the clinical feasibility of human osmotic BBBD suggest that this approach may be adopted to treat brain or spinal cord tumors. In addition, BBBD may favor CNS entry of other cells that normally lack CNS tropism.

2005-06-03·Journal of Leukocyte Biology3区 · 医学

Receptors and lytic mediators regulating anti-tumor activity by the leukemic killer T cell line TALL-104

3区 · 医学

Article

作者: Medina, Rosa ; Catina, Tracey L ; Mukhopadhyay, Sunil ; Patel, Pritesh ; Brando, Clara ; Santoli, Daniela ; Kovacs, Eniko ; Campbell, Kerry S

AbstractThe major histocompatibility complex nonrestricted cytotoxic leukemic T cell line T acute lymphoblastic leukemia (TALL)-104 is being pursued as a therapeutic agent for cancer. However, the receptors and effector mechanisms responsible for its broad tumoricidal function remain undefined. Here, we examined the roles played by natural cytotoxicity receptors (NCR), killer cell immunoglobulin-like receptors, cytolytic granule components, and tumor necrosis factor (TNF) family members in tumor recognition and lysis by TALL-104 cells. The perforin-granzyme pathway, TNF-related apoptosis-inducing ligand (TRAIL), and Fas were each involved in the lysis of particular tumor targets by TALL-104. Furthermore, phorbol 12-myristate 13-acetate/ionomycin treatment induced surface expression of Fas-L and TRAIL. In addition, supernatants from CD3-stimulated TALL-104 cultures exhibited antiproliferative activity, which was blocked 50–90% by anti-TNF-α monoclonal antibody (mAb). Although negative for the NCR natural killer (NK)p44, this cell line was found to express NKp46. An anti-NKp46 antibody strongly blocked TALL-104-mediated lysis of certain targets and directly induced cytokine production, granule release, and redirected lysis responses. Anti-NKG2D and anti-2B4 also stimulated redirected cytotoxicity by TALL-104. By contrast, anti-NKG2A mAb did not stain the cells or inhibit killing responses. Alternatively, KIR3DL2 was detected on TALL-104, and expression of its reported ligand, human leukocyte antigen (HLA)-A, on target cells provided protection from cytotoxicity. Thus, NKp46, NKG2D, and 2B4 are activating receptors, and KIR3DL2 is an inhibitory receptor on TALL-104. The data demonstrate the ability of TALL-104 cells to recognize a wide variety of tumors with NK cell receptors and kill them with a broad arsenal of cytolytic effector mechanisms, including cytolytic granules and TNF family ligands.

2000-10-15·Cancer research

The human leukemic T-cell line, TALL-104, is cytotoxic to human malignant brain tumors and traffics through brain tissue: implications for local adoptive immunotherapy.

Article

作者: Kruse, C A ; Visonneau, S ; Santoli, D ; Gup, C J ; Gomez, G G ; Paul, D B ; Kleinschmidt-DeMasters, B K

Preclinical studies with the human MHC nonrestricted cytotoxic T-cell leukemic line, TALL-104, were performed in anticipation of its use in cellular immunotherapy trials for primary malignant brain tumors. In this study, we have: (a) quantitated the in vitro brain tumor cell lysis; (b) measured the cytokine secretion upon coincubation of TALL-104 cells with brain tumor cells; (c) investigated the effect of dexamethasone on brain tumor cell cytolysis by TALL-104 cells; (d) explored the effects of lethal irradiation and cryopreservation on TALL-104 cell viability and lytic efficacy; and (e) estimated the damage TALL-104 cells induce to murine normal and tumor brain cells and their trafficking patterns in both normal and tumor-bearing rat brain upon intracranial infusion. In vitro coincubation of TALL-104 cells with human brain tumor cells, explants, and cell lines resulted in significant lysis of them, but normal brain cells were spared. Lysis of tumor at 4 h was unaffected by dexamethasone or lethal irradiation. Secretion of tumor necrosis factor-alpha, tumor necrosis factor-beta, IFN-gamma, or granulocyte/macrophage-colony stimulating factor upon TALL-104 cell coincubation with brain tumor cells variably occurred without always correlating with lysis. In vivo experiments using irradiated TALL-104 cells, placed at multiple times into normal cannulated rat brain, produced focal sterile abscesses at the instillation site but no widespread allergic encephalitic reaction. Cells morphologically consistent with TALL-104 cells specifically trafficked from the site of instillation through the neuropil, occasionally into the contralateral brain, and egressed at perivascular and leptomeningeal spaces. In vivo experiments with cannulated rats bearing 9L gliosarcoma showed a preferential localization of the TALL-104 cells in tumor compared with normal brain. Taken together, these data support the concept that TALL-104 cells can be used as a novel nontoxic and efficacious paradigm for cellular immunotherapy trials in human primary malignant brain tumors.

100 项与 TALL-104 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
卵巢上皮癌	临床2期	意大利	Galileo Research Srl	2015-04-25
白血病	临床2期	美国	The University of Texas MD Anderson Cancer Center	2015-03-03
淋巴瘤	临床2期	美国	The University of Texas MD Anderson Cancer Center	2015-03-03
慢性期慢性髓性白血病	临床2期	美国	Abiogen Pharma SpA	2006-12-01
腹膜癌	临床2期	意大利	Galileo Research Srl	-

登录后查看更多信息

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


NCT02210065 (CTgov)	临床2期	白血病 \| 淋巴瘤	6	Cytomegalovirus (CMV)-Specific Cytotoxic T Cells (CTLs)	窪廠糧獵範築鹹壓選遞(製鏇鹹鬱襯糧廠膚選鬱) = 窪築範顧選淵鑰蓋願願廠蓋製顧鑰餘糧衊鹽積 (鑰鹽遞膚衊範齋醖膚膚, 衊範鏇網鹹糧餘鹹繭鬱 ~ 夢鬱鑰糧廠繭醖製願蓋) 更多	-	2020-03-17
NCT00415909 (CTgov)	临床2期	慢性期慢性髓性白血病	3	Imatinib Mesylate (IM)+TALL-104 cells	選鏇獵糧壓糧遞築蓋選(積觸鏇淵積範夢鏇鑰築) = 範繭淵夢夢簾淵壓醖憲願顧襯蓋膚網範蓋鑰繭 (鏇簾憲艱鏇遞積廠醖鏇, 廠顧鑰鑰壓構觸選繭選 ~ 壓鑰糧簾膚鏇積醖淵鹽) 更多	-	2014-06-30