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-

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

EU (18 Aug 2016),

Hematologic NeoplasmsHematopoietic stem cell transplantation

Regulation-

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Gene 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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538

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·International Journal of Radiation Oncology*Biology*Physics

A Phase 2 Study of In Situ Oncolytic Virus Therapy and Stereotactic Body Radiation Therapy Followed by Pembrolizumab in Metastatic Non-Small Cell Lung Cancer

Article

Author: Chen, Shu Hsia ; Guerrero, Carlo A ; Mejia, Jaime ; Zhang, Jun ; Zheng, Junjun ; Mathur, Sunil ; Chang, Jenny C ; Zsigmond, Eva ; Teh, Bin S ; Sun, Kai ; Butler, Edward ; Mei, Zhuyong ; Pan, Ping-Ying ; Xu, Yitian ; Guan, Jian ; Farach, Andrew ; Bernicker, Eric H

PURPOSEA phase 2 study of stereotactic body radiation therapy (SBRT) and in situ oncolytic virus therapy in metastatic non-small cell lung cancer (mNSCLC) followed by pembrolizumab (STOMP) was designed to explore the dual approach in enhancing single pembrolizumab with ADV/HSV-tk plus valacyclovir gene therapy and SBRT in mNSCLC.METHODS AND MATERIALSSTOMP is a single-arm, open-label phase 2 study. Patients with mNSCLC received intratumoral injections of ADV/HSV-tk (5 × 10¹¹ vp) and SBRT (30 Gy in 5 fractions) followed by pembrolizumab 200 mg IV every 3 weeks until disease progression or intolerable toxicity. The primary endpoint was overall response rate (ORR) (complete response [CR] and partial response [PR]). Secondary endpoints included clinical benefit rate (CBR) (CR, PR and stable disease [SD]), progression-free survival (PFS), overall survival (OS), and safety.RESULTS28 patients were enrolled, of whom 27 were evaluated for response. The ORR was 33.3%, including 2 CR (7.4%) and 7 PR (25.9%). CBR was 70.4%. Six of eight (75.0%) patients who were immune checkpoint inhibitor (ICI) refractory derived clinical benefits. Responders had durable responses with median PFS, and OS not reached. The entire cohort had a median PFS of 7.4 months (95% CI, 5.1-9.6 months), and median OS of 18.1 months (95% CI, 15.4-20.9 months). The combination was well tolerated, with grade 3 or higher toxicity in 6 (21.4%) patients.CONCLUSIONSThe dual approach of in situ ADV/HSV-tk plus valacyclovir gene therapy and SBRT as a chemotherapy-sparing strategy to enhance the antitumor effect of pembrolizumab is a well-tolerated encouraging treatment in patients with mNSCLC.

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 ; Qi, Qibin ; Clish, Clary ; 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 Jan 2024·Journal of Ultrasound in Medicine

Nanotargeted Cationic Lipid Microbubbles Carrying HSV‐TK Gene Inhibit the Development of Subcutaneous Liver Tumor Model After HIFU Ablation

Article

Author: Du, Di ; Lai, Xing ; Gu, Xue ; Zhang, Yudi ; Liu, Yan ; Zhang, Xian ; Hong, Guoqing

ObjectivesHigh‐intensity focused ultrasound (HIFU) has been widely used in clinical settings and has achieved suitable results in the treatment of many cancerous or noncancerous diseases. However, in the treatment of liver cancer, because the tumor is located deep within the liver tissue, when ultrasound penetrates the tissue, it will inevitably produce sound energy attenuation. This attenuation limits the reliability of HIFU treatment, reduce the efficacy of HIFU, and increase the risk of tumor recurrence.MethodsCationic microbubbles (CMB) were successfully linked with GPC3 and HSV‐TK plasmids, and targeted gene‐carrying CMB were successfully constructed. Moreover, the gene‐targeted cation microbubbles had suitable targeting and can specifically bind with liver cancer cells.ResultsThe HSV‐TK transfection efficiency was high and had a significant inhibitory effect on the proliferation and invasion of liver cancer cells. After the gene‐carrying cation microbubbles entered the animal body, they had a great targeting effect in vivo. They transfected the target genes into liver cancer cells, and the HSV‐TK/GCV system initiated cell death, demonstrating that these targeted microbubbles, enhanced HIFU treatment.ConclusionsOverall, CMB combined with a GPC3 antibody and HSV‐TK plasmid can target residual subcutaneous liver tumor cells under the guidance of GPC3 antibody, and kill residual subcutaneous liver tumor cells under the action of ultrasound, thus enhancing the therapeutic effect of HIFU on liver cancer.

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	(dpemlcehpa) = 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. fcgpevekwb (gigoakskrr )	Positive	01 May 2002