Drug Database
HS

HSV-tk gene therapy (HSVtk / Zalmoxis / TK therapy)

✓ Approved

Megapharm Ltd · POLA1 · Cell-based Therapies

What is HSV-tk gene therapy?

HSV-tk gene therapy is a cell-based therapies developed by Megapharm Ltd. It is approved for therapeutic indications via injectable (others) or intravenous (iv).

Drug Profile

Brand NamesHSVtk, Zalmoxis, TK therapy
CompanyMegapharm Ltd
Drug ClassCell-based Therapies, Gene Therapy
Molecular TargetPOLA1
RouteInjectable (Others), Intravenous (IV)
StatusApproved
Sources: ClinicalTrials.gov, Megapharm Ltd

Mechanism of Action

Molecular Targets

HSV-tk gene therapy acts on 1 molecular target:

POLA1DNA polymerase alpha 1, catalytic subunit (PDR, POLA)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

HSV-tk gene therapy is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Immune system disordersChronic graft versus host disease✓ Approved

Related Research Articles

PubMedIn vitro models2026-09-20

Pathophysiology and biomaterials based therapeutic strategies for spinal muscular atrophy.

Nasser Aya Ayman AA, Nasser Rasha Ayman RA, Singh Hemant H, Veettil Rukshana Mangattu RM et al.

Spinal muscular atrophy (SMA) is a disorder characterized by the degeneration of lower motor neurons caused by mutations in the survival motor neuron 1 (SMN1) gene on chromosome 5. These mutations lead to a decline in SMN protein levels, which contributes to the development of this disease. SMA is an autosomal recessive disorder that results in intensified weakness in respiratory and skeletal muscles, leading to severe disability. Understanding the pathophysiology and etiology of the disease paves a clear path for scientists in developing and advancing treatment approaches for this condition. This review article provides an overview of SMA, encompassing the characteristics of the disease, standard-of-care techniques, including respiratory care and physiotherapy, and existing treatments and recent advancements in novel therapeutic strategies and biomaterials for SMA. Several limitations associated with the existing SMA treatment methods are also discussed. The review highlights significant progress in SMA therapy, including gene replacement therapies, antisense oligonucleotides, and small-molecule drugs that enhance SMN protein production. Despite these advancements, current treatments face limitations related to delivery efficiency, cost, and long-term efficacy. Novel biomaterials and delivery systems show promise in overcoming these challenges and improving treatment outcomes. A deeper understanding of SMA pathophysiology has led to transformative therapeutic advances; however, challenges remain in optimizing treatment accessibility, durability, and safety. Continued research focusing on innovative therapeutic designs and biomaterial applications holds potential to further enhance the quality of life and prognosis for individuals with SMA.

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PubMedCureus2026-09-20

A Greek Real-World Experience With the Implementation of the EndoPredict Gene Signature in a Cohort of Pre-menopausal and Post-menopausal Patients With ER+/HER2- Breast Cancer.

Pantazidis George G, Sourla Antigoni A, Vasiageorgi Aggeliki A, Yfanti Christina C et al.

Background EndoPredict® is a guideline-recommended gene signature assay guiding whether adjuvant treatment should include chemotherapy or not. The EndoPredict® Clinical (EPclin) Risk Score combines molecular and clinical data to predict the distant recurrence of breast cancer, providing valuable information about the prognosis and chemotherapy benefit in both pre- and post-menopausal patients. Methodology This is a real-world, retrospective study aiming to characterize the EPclin Risk Score's utility in 200 consecutively selected Greek patients with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) breast cancer, enrolled in a single institution, considering their clinicopathological features and menopausal status, with emphasis on its role in identifying patients suitable for treatment de-escalation. Results In this study, 100 pre-menopausal and 100 post-menopausal ER+/HER2- breast cancer patients were included. Among the pre-menopausal subgroup, 65% of the patients were classified as low risk and the other 35% as high risk, while among the post-menopausal subgroup, the low-risk and high-risk patients were 66% and 34%, respectively. A notable 30% of node-positive premenopausal patients were characterized by EPclin as at a low risk of breast cancer. Conclusions The EPclin Risk score has the ability to stratify and guide therapy decisions in ER+/HER2- breast cancer patients. It classifies the recurrence risk differently from traditional assessments and identifies low-risk premenopausal patients with node-positive disease. This may provide a de-escalation treatment pathway for such patients but requires further clinical validation.

PMID 42763779
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PubMedImmunoTargets and therapy2026-09-20

A Myeloid-Specific Endogenous TRP1-CAR Knock-in Mouse Model for Melanoma-Targeted Immunotherapy.

Hao Yuxin Y, Chen Xin X, Wang Min M, Han Jinxiang J et al.

Malignant melanoma is highly aggressive and prone to therapeutic resistance. Chimeric antigen receptor macrophage (CAR-M) therapy is promising for solid tumors, but conventional ex vivo-engineered CAR-M has limited in vivo persistence, complicating longer-term safety evaluation. This study established a myeloid-specific, endogenously expressed tyrosinase-related protein 1 (TRP1)-CAR mouse model to assess antitumor activity and safety. TRP1-CAR was conditionally knocked into the Rosa26 locus and crossed with Lysozyme 2 (Lyz2)-Cre mice to generate mice with myeloid-specific TRP1-CAR expression (TRP1-CARM). CAR signals and baseline observations were assessed by flow cytometry, tissue immunofluorescence, histopathology, and hematology. Phagocytosis, cytotoxicity, and inflammation-related gene expression were evaluated in vitro. A syngeneic B16-Fluc-GFP melanoma model was used in two independent cohorts to assess tumor growth, survival, intratumoral CD8+ T-cell infiltration, and histopathology. CAR signals were detected in peripheral blood and in F4/80-positive macrophage-containing areas of the lung, liver, and spleen. No overt histopathological abnormalities or hematological changes were observed in the tissues examined under baseline conditions. TRP1-CARM-BMDMs showed enhanced phagocytic and cytotoxic activity against B16-Fluc-GFP cells, accompanied by altered inflammation-related gene expression in the co-culture system. In vivo, TRP1-CARM mice showed delayed tumor growth (P < 0.0001) and prolonged survival (P = 0.0005), with increased intratumoral CD8+ T-cell infiltration. This myeloid-specific TRP1-CAR knock-in model showed in vitro antitumor activity and delayed melanoma progression in vivo. It provides a proof-of-concept framework for investigating antitumor activity and preliminary safety observations associated with sustained endogenous CAR expression.

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PubMedMediastinum (Hong Kong, China)2026-09-20

Novel strategies in radiation therapy: high-dose radiotherapy for oligometastatic/oligo-progressive thymic tumors.

Alaverdashvili Tinatin T, Rimner Andreas A

Oligometastatic and oligoprogressive thymic tumors are unique clinical presentations that are generally rare, yet occur with some regularity, especially in large volume centers. Close observation is often a viable option at first. Surgical resection is usually the primary local therapy approach whenever possible based on technical resectability and patient's medical operability. High-dose radiation therapy has opened more opportunities for patients who may need adjuvant radiation therapy to further optimize local tumor control in addition to surgery or definitive therapy, or in place of surgical resection when surgery may be difficult or impossible due to tumor- or patient-related factors, with high local control rates in appropriately selected patients. Especially in the metastatic setting, long-term effects of therapy and quality of life need to be balanced against local tumor control and survival endpoints. The excellent ratio of high efficacy and low risk of adverse events with high-dose stereotactic body radiation therapy and intensity-modulated radiation therapy make this radiation technique a particularly attractive treatment approach for optimizing local control and quality of life. A deep understanding of the strengths and weaknesses of each treatment modality are critical to allow for optimal use and integration of local and systemic treatment options. Here, we review the newest data for the role of local therapies in oligometastatic, oligoresidual and oligoprogressive thymic tumors with a focus on the development of high-dose radiation therapy techniques.

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PubMedBritish journal of cancer2026-09-20

TSPAN32 enhances CAR-T cell potency by assembling IL-2 receptor complex and amplifying its intracellular signal transduction.

Sun Yuanyuan Y, Qiu Qiang Q, Wang Bochuan B, Feng Yunyu Y et al.

Chimeric antigen receptor-engineered T cells (CAR-T) have shown substantial therapeutic potential in hematologic malignancies, but further improvement in T-cell functional capacity is needed to optimize efficacy. We observed reduced TSPAN32 expression in T cells from peripheral blood of patients with B-cell lymphoma. This study aimed to investigate whether TSPAN32 enhances CAR-T cell antitumor activity and to explore the underlying mechanism. TSPAN32 expression was assessed in T cells isolated from patients with B-cell lymphoma. T cells were engineered to co-express TSPAN32 and CD19-CAR, and their antitumor efficacy and cytokine secretion were evaluated in vitro and in subcutaneous tumor models in vivo. Gene expression profiling was performed to identify signaling pathways associated with TSPAN32 overexpression. Mechanistic studies examined the interaction between TSPAN32 and CD25 and its effect on IL-2 signaling. In addition, a transgenic mouse model with endogenous TSPAN32 overexpression and a TSPAN32-specific antibody (FF-37) were used to assess therapeutic potential. TSPAN32 expression was reduced in T cells from B-cell lymphoma patients. Co-expression of TSPAN32 with CD19-CAR significantly enhanced antitumor activity and cytokine production compared with CD19-CAR alone in vitro. In vivo, T cells engineered with both CAR and TSPAN32 showed superior therapeutic efficacy in subcutaneous tumor models. Gene expression profiling indicated increased IL-2 signaling activation in TSPAN32-high CAR-T cells. Mechanistically, TSPAN32 interacted with CD25, promoting its aggregation on the T-cell surface and enhancing IL-2 signal transduction. Endogenous TSPAN32 overexpression in transgenic mice increased resistance to subcutaneous tumor growth. Furthermore, the TSPAN32-specific antibody FF-37 increased TSPAN32 expression and improved CAR-T antitumor efficacy. TSPAN32 enhances CAR-T cell antitumor function by promoting CD25 aggregation and IL-2 signaling activation. Increasing TSPAN32 expression, either through genetic engineering or the TSPAN32-specific antibody FF-37, may represent a promising strategy to improve CAR-T cell therapy.

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PubMedAdvances in virology2026-09-20

Comparative Sequence Analysis of the Envelope Gene of Kyasanur Forest Disease Virus Vaccine Strain With Currently Circulating Field Strains.

Kaje Keerthi K, Marinaik Chandranaik B CB, Gomes Amitha Reena AR, Rizwan Apsana A et al.

The present study was undertaken with the objective of performing comparative sequence analysis of the envelope (E) gene of Kyasanur forest disease virus (KFDV) vaccine strain P9605 with the circulating field strains. The study was taken up as the currently used KFDV vaccine strain, KFDV P9605, was isolated in the 1960s. For this study, we designed two sets of primers targeting the complete amplification of the E gene of KFDV. The sequencing was performed by the Sanger method, and the deduced sequence of the vaccine virus was deposited in GenBank with accession number PX067005. This sequence obtained for the vaccine virus was aligned and compared with sequences of GenBank-deposited circulating field strains. We also performed comparative sequence analysis of the Kyasanur forest disease (KFD) vaccine seed virus having passaged twice in mouse brain with the vaccine seed virus passaged six times in mouse brain to investigate whether multiple passages in mouse brain will lead to genetic mutation in the immunologically important E gene. The phylogenetic analysis revealed seven amino acid mutations in the field strains at positions A123T, S158N, D178E, D239N, A313S, M429I, and G479A when compared with the vaccine strain. We did not find any mutations at the critical fusogenic segment (residues 98-113) in the E gene of currently circulating field strains compared to the vaccine seed virus. The study found no genetic variations in the E gene of the KFD virus passed two times and passed six times in mouse brain. We performed SWISS-MODEL homology modeling, AlphaFold protein analysis, and Ramachandran plot analysis to study the E protein structures and stability. The observations made in this study suggest slow evolutionary drift and conserved structural stability of the envelope gene of KFDV ever since its emergence 7 decades ago; however, the functional implications of these amino acid substitutions need further studies on their roles in viral infectivity, transmission, and impact on immunity.

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