Delving into the Latest Updates on Allogeneic T cells genetically modified with a retroviral vector encoding for a truncated form of the human low affinity nerve growth factor receptor (ΔLNGFR) and the herpes simplex I virus thymidine kinase (HSV-TK Mut2) with Synapse

Overview

Basic Info

Drug Type

T-lymphocyte cell therapy

Synonyms

HSV-Tk, Herpes simplex virus thymidine kinase (HSV-Tk) donor lymphocytes, TK

+ [5]

Target-

Action

stimulants

Mechanism

Cell replacements, Immunostimulants

Therapeutic Areas

NeoplasmsHemic and Lymphatic DiseasesOther Diseases

Active Indication-

Inactive Indication

Hematologic NeoplasmsHematopoietic stem cell transplantation

Originator Organization

AGC Biologics SpA

Active Organization-

Inactive Organization

AGC Biologics SpA

Drug Highest PhaseWithdrawn

First Approval Date

European Union (18 Aug 2016),

Hematologic NeoplasmsHematopoietic stem cell transplantation

Regulation-

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Structure/Sequence

Sequence Code 1183843821

Source: *****

The purpose of this study is to conduct a Phase I - II clinical trial to extend preclinical studies involving in situ HSV-tk + Valacyclovir gene therapy in combination with brachytherapy for recurrent prostate cancer. This will provide a novel therapeutic approach to prostate cancer and hopefully impact on the development of metastatic disease and the control of preexisting metastasis.

Start Date01 Jun 2007

Sponsor / Collaborator

The Methodist Hospital Research Institute

100 Clinical Results associated with Allogeneic T cells genetically modified with a retroviral vector encoding for a truncated form of the human low affinity nerve growth factor receptor (ΔLNGFR) and the herpes simplex I virus thymidine kinase (HSV-TK Mut2)

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100 Translational Medicine associated with Allogeneic T cells genetically modified with a retroviral vector encoding for a truncated form of the human low affinity nerve growth factor receptor (ΔLNGFR) and the herpes simplex I virus thymidine kinase (HSV-TK Mut2)

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100 Patents (Medical) associated with Allogeneic T cells genetically modified with a retroviral vector encoding for a truncated form of the human low affinity nerve growth factor receptor (ΔLNGFR) and the herpes simplex I virus thymidine kinase (HSV-TK Mut2)

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99

Literatures (Medical) associated with Allogeneic T cells genetically modified with a retroviral vector encoding for a truncated form of the human low affinity nerve growth factor receptor (ΔLNGFR) and the herpes simplex I virus thymidine kinase (HSV-TK Mut2)

01 Apr 2024·Journal of NeuroVirology

Tryptophan-kynurenine metabolic pathway and daytime dysfunction in women with HIV

Article

Author: Sharma, Anjali ; Daubert, Elizabeth ; Burgess, Helen J ; Yohannes, Tsion ; Clish, Clary ; Qi, Qibin ; Gustafson, Deborah ; Rogando, Andrea C ; Shorer, Eran Frank ; Bullock, Kevin ; Morack, Ralph ; Dastgheyb, Raha M ; French, Audrey L ; Rubin, Leah H ; Weber, Kathleen M

Sleep disturbances are prevalent in women with HIV (WWH). Tryptophan-kynurenine (T-K) pathway metabolites are associated with alterations in actigraphy derived sleep measures in WWH, although may not always correlate with functional impairment. We investigated the relationship between T-K pathway metabolites and self-reported daytime dysfunction in WWH and women without HIV (WWoH). 141 WWH on stable antiretroviral therapy and 140 demographically similar WWoH enrolled in the IDOze Study had targeted plasma T-K metabolites measured using liquid chromatography-tandem mass spectrometry. We utilized the daytime dysfunction component of the Pittsburgh Sleep Quality Index (PSQI) to assess functional impairment across HIV-serostatus. Lower levels of 5-hydroxytryptophan and serotonin were associated with greater daytime dysfunction in all women. In WWH, daytime dysfunction was associated with increased kynurenic acid (R = 0.26, p < 0.05), and kynurenic acid-tryptophan (KA-T) ratio (R = 0.28, p < 0.01). WWH with daytime dysfunction had a 0.7 log fold increase in kynurenic acid compared to WWH without daytime dysfunction. Kynurenic acid levels and the KA-T ratio were associated with daytime dysfunction in WWH but not in WWoH. Longitudinal studies are needed to establish a causal relationship and directionality between T-K metabolic changes and sleep impairment in WWH.

01 Sep 2022·Molecular Therapy - Oncolytics

β2-Adrenergic receptor agonist enhances the bystander effect of HSV-TK/GCV gene therapy in glioblastoma multiforme via upregulation of connexin 43 expression

Article

Author: Dehpour, Ahmad Reza ; Javadi, Seyed Amirhossein ; Hadjighassem, Mahmoudreza ; Fallah, Ali ; Hosseindoost, Saereh ; Arjmand, Babak ; Mousavi, Seyed Mojtaba

Glioblastoma multiforme (GBM) is the most invasive form of primary brain astrocytoma. Gene therapy using the herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) is a new strategy for GBM treatment. As the connexin 43 (Cx43) levels are downregulated in GBM cells, it seems that the upregulation of Cx43 could improve the efficacy of the gene therapy. This study aims to evaluate the effect of clenbuterol hydrochloride (Cln) as a β2-adrenergic receptor agonist on HSV-TK/GCV gene therapy efficacy in human GBM cells using olfactory ensheathing cells (OECs) as vectors. The lentivirus containing the thymidine kinase gene was transduced to OECs and the effective dose of GCV on cells was measured by MTT assay. We found that Cln upregulated Cx43 expression in human GBM cells and OECs and promoted the cytotoxic effect of GCV on the co-culture cells. Western blot results showed that Cln increased the cleaved caspase-3 expression and the Bax/Bcl2 ratio in the co-culture of GBM cells and OEC-TK. Also, the flow cytometry results revealed that Cln increased apoptosis in the co-culture of GBM cells and OEC-TK cells. This study showed that Cln via upregulation of Cx43 expression could enhance the bystander effect of HSVTK-GCV gene therapy in human GBM cells.

01 Aug 2022·Food Research International

Protective effects of Tibetan kefir in mice with ochratoxin A-induced cecal injury

Article

Author: Yuan, Yahong ; Yue, Tianli ; Yan, Xiaohai ; Shi, Kehan ; Guo, Qi ; Chang, Shuaidan ; Du, Gengan ; Chen, Hong

Ochratoxin A (OTA) is reported to cause intestinal damage following ingestion of contaminated foods. Tibetan kefir (TK) is a fermented dairy product that possesses antioxidant, anti-inflammatory, and gut microbiota-regulating properties. However, it is not clear if TK can alleviate OTA-associated intestinal toxicity. Here, we investigated whether TK can prevent OTA-induced intestinal barrier disruption in mice. To this end, OTA-fed mice were treated with sterile water (control) or TK by oral gavage once daily, for 3 weeks. The histological changes of ceca, the expression of tight junction proteins and mucins, and the levels of oxidative stress, inflammatory response, and gut microbiota were then assessed. Results revealed that treatment with TK reversed OTA-driven histopathological changes in the ceca, and was associated with increased cecal mucin levels. TK administration to OTA-treated mice significantly elevated the expression levels of tight junction proteins (claudin-1, zonula occludens-1, and occludin). Additionally, TK supplementation suppressed OTA-induced oxidative stress and reduced inflammation via the NF-κB signaling pathway in the ceca. Moreover, TK supplementation depleted harmful bacteria (e.g., Turicibacter and Desulfovibrio), while supporting short-chain fatty acids (SCFAs)-producing bacteria (e.g., Lachnospiraceae, Blautia, and Ruminococcus), which maintained the SCFAs levels. Taken together, our findings indicate that TK may emerge as a viable dietary strategy to prevent intestinal toxicity-based injuries.

100 Deals associated with Allogeneic T cells genetically modified with a retroviral vector encoding for a truncated form of the human low affinity nerve growth factor receptor (ΔLNGFR) and the herpes simplex I virus thymidine kinase (HSV-TK Mut2)

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External Link

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R&D Status

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASGCT2002	Not Applicable	Hematopoietic stem cell transplantation \| Graft vs Host Disease	8	HSV-TK Engineered Donor Lymphocytes (Tk-DLI)	uaefzpcjmx(wsozzdleay) = 1/8 patients experienced grade II biopsy-proven acute GvHD, involving the skin and the liver. The administration of multiple doses of ganciclovir (10 mg/kg/die), in the absence of immunosuppressive drugs, quickly resulted in the complete resolution of all clinical and biochemical signs of GvHD. Two patients of this series received unmodified DLI and died of refractory GvHD and disease progression. jebmbgnnpi (vuxsmklgjh )	Positive	01 May 2002