Delving into the Latest Updates on TALL-104 with Synapse

Overview

Basic Info

Drug Type

T-lymphocyte cell therapy

Synonyms

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

+ [1]

Target-

Action

stimulants

Mechanism

Cell death stimulants, Immunologic cytotoxicity, T lymphocyte replacements

Therapeutic Areas

NeoplasmsEndocrinology and Metabolic DiseaseHemic and Lymphatic Diseases+ [2]

Active Indication-

Inactive Indication

Chronic phase chronic myeloid leukemiaOvarian Epithelial CarcinomaPeritoneal Neoplasms+ [1]

Originator Organization

The Wistar Institute

Active Organization-

Inactive Organization

Galileo Research Srl

The University of Texas MD Anderson Cancer Center

Abiogen Pharma SpA

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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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.

Start Date03 Mar 2015

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+1]

NCT00415909

/ TerminatedPhase 2IIT

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.

Start Date01 Dec 2006

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+1]

100 Clinical Results associated with TALL-104

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100 Translational Medicine associated with TALL-104

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100 Patents (Medical) associated with TALL-104

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18

Literatures (Medical) associated with TALL-104

01 Dec 2010·BMC NeuroscienceQ3 · MEDICINE

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

Q3 · MEDICINE

ArticleOA

Author: 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.

03 Jun 2005·Journal of Leukocyte BiologyQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: Medina, Rosa ; Mukhopadhyay, Sunil ; Catina, Tracey L ; 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.

15 Oct 2000·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

Author: 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 Deals associated with TALL-104

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Ovarian Epithelial Carcinoma	Phase 2	Italy	Galileo Research Srl	25 Apr 2015
Chronic phase chronic myeloid leukemia	Phase 2	United States	Abiogen Pharma SpA	01 Dec 2006
Peritoneal Neoplasms	Phase 2	Italy	Galileo Research Srl	-
Philadelphia chromosome positive chronic myelogenous leukemia	Phase 2	United States	The University of Texas MD Anderson Cancer Center	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02210065 (CTgov)	Phase 2	Leukemia \| Lymphoma	6	Cytomegalovirus (CMV)-Specific Cytotoxic T Cells (CTLs)	abwuupjomm(yevysjfnyr) = uzihchmwxq fpneriebdu (vseqrdzjes, hqclpzzgzl - emiezeapaj) View more	-	17 Mar 2020
NCT00415909 (CTgov)	Phase 2	Chronic phase chronic myeloid leukemia	3	Imatinib Mesylate (IM)+TALL-104 cells	girnsrqjxp(vpjmrxcwrc) = muhaqkjkov ktqjfmysol (kfihdtutro, mtjfvitukj - wgppssrjmy) View more	-	30 Jun 2014