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

License Organization

AGC Biologics SpA

Megapharm Ltd.

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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46

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 ; Dastgheyb, Raha M ; Morack, Ralph ; 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 Jun 2022·Biomedicine & PharmacotherapyQ2 · MEDICINE

Dioscin potentiates the antitumor effect of suicide gene therapy in melanoma by gap junction intercellular communication-mediated antigen cross-presentation

Q2 · MEDICINE

Article

Author: Lin, Lingyun ; Wang, Huiqi ; Zhan, Yujuan ; Zhang, Yujian ; Zhang, Wenbo ; Du, Biaoyan ; Zhao, Tingxiu ; Fang, Junfeng

Dioscin (Dio), steroid saponin, exists in several medicinal herbs with potent anticancer efficacy. This study aimed to explore the effect of Dio on the immune-related modulation and synergistic therapeutic effects of the herpes simplex virus thymidine kinase/ganciclovir (HSV-Tk/GCV) suicide gene therapy system in murine melanoma, thereby providing a research basis to improve the potential immunomodulatory mechanism underlying combination therapy. Using both in vitro and in vivo experiments, we confirmed the immunocidal effect of Dio-potentiated suicide gene therapy on melanoma. The results showed that Dio upregulated connexin 43 (Cx43) expression and improved gap junction intercellular communication (GJIC) in B16 cells while increasing the cross-presentation of antigens by dendritic cells (DCs), eventually promoting the activation and antitumor immune killing effects of CD8⁺ T lymphocytes. In contrast, inhibition or blockade of the GJIC function (overexpression of mutant Cx43 tumor cells/Gap26) partially reversed the potentiating effect. The significant synergistic effect of Dio on HSV-Tk/GCV suicide gene therapy was further investigated in a B16 xenograft mouse model. The increased number and activation ratio of CD8⁺ T lymphocytes and the levels of Gzms-B, IFN-γ, and TNF-α in mice reconfirmed the potential modulatory effects of Dio on the immune system. Taken together, Dio targets Cx43 to enhance GJIC function, improve the antigens cross-presentation of DCs, and activate the antitumor immune effect of CD8⁺ T lymphocytes, thereby providing insights into the potential immunomodulatory mechanism underlying combination therapy.

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

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hematologic Neoplasms	Phase 2	European Union	AGC Biologics SpA	18 Aug 2016
Hematologic Neoplasms	Phase 2	Iceland	AGC Biologics SpA	18 Aug 2016
Hematologic Neoplasms	Phase 2	Norway	AGC Biologics SpA	18 Aug 2016
Hematologic Neoplasms	Phase 2	Liechtenstein	AGC Biologics SpA	18 Aug 2016

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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)	pqrolvvvjt(ykbigrerya) = 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. abubrnsjpd (qftsdoatql )	Positive	01 May 2002