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

PubMedFrontiers in immunology2026-10-15

Oncolytic virus VT1092M synergizes with immune checkpoint inhibitors against intraperitoneal metastases of colorectal cancer.

Hu Zongfeng Z, Yuan Xinru X, Li Shuzhen S, Liu Wenqi W et al.

Intraperitoneal metastasis is a frequent progression in colon cancer, highlighting the critical need for enhanced therapeutic approaches. Oncolytic virus (OV) therapy has emerged as a promising immunotherapeutic strategy. The combination of OVs with immune checkpoint inhibitors (ICIs) has demonstrated an enhanced anti-tumor response. We generated the intraperitoneal-subcutaneous bilateral colon cancer xenograft model to simulate intraperitoneal metastatic colon cancer, and evaluated the systemic antitumor efficacy of the oncolytic HSV-1 virus VT1092M in combination with ICIs (anti-PD-L1 antibody and anti-CTLA-4 antibody). Intraperitoneal administration of VT1092M markedly suppressed intraperitoneal cancer progression and enhanced the superior antitumor efficacy of ICIs immunotherapy in murine intraperitoneal metastatic colon cancer. Notably, treatment of VT1092M combined with anti-CTLA-4 antibody could eliminate both intraperitoneal metastases and subcutaneous tumors, while also inhibiting the formation of peritoneal blood vessels and malignant ascites. The synergistic combination of VT1092M and anti-CTLA-4 elicited potent intraperitoneal and systemic antitumor immunity, culminating in durable, tumor-specific memory that significantly prolonged survival in mice with colorectal intraperitoneal metastases compared to either monotherapy. Mechanistically, the combination therapy activates the anti-tumor immune environment within the peritoneal cavity, leading to a significant increase in tumoricidal CD8+ T cells and M1 macrophages, as well as the reprogramming of transcriptional signatures associated with the tumor immune response within the tumor microenvironment. Ultimately, intraperitoneal immunotherapy with VT1092M enhances the efficacy of immune checkpoint blockade in suppressing intraperitoneal metastatic colorectal cancer and induces durable tumor-specific immune memory, thereby exerting substantial anti-tumor effects. This finding highlights the potential of synergistically combining oncolytic viruses with ICIs to advance immunotherapeutic strategies for intraperitoneal metastatic colorectal cancer.

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PubMedHuman gene therapy2026-10-15

Beyond Viruses: Transposons and CRISPR-Programmable Nonviral Systems for Genome Engineering.

Singh Satnam S, Panchal Omkar Vikram OV, Ivics Zoltán Z

Human gene therapy has been transformed by repurposing mobile genetic elements as tools for efficient gene delivery and precise genome modification. Viruses, transposons, and retrotransposons mobilize genetic material through distinct mechanisms with distinct advantages for genome engineering platforms with therapeutic potential. This review describes the mechanisms, performance characteristics, and translational relevance of nonviral methods of gene transfer and genome engineering, with emphasis on engineered systems such as the Sleeping Beauty (SB) and piggyBac (PB) DNA transposons, R2 retrotransposon-based platforms, CRISPR-associated transposons (CASTs), and prime editing (PE). Clinical trials using both SB- and PB-engineered cells have shown feasibility by demonstrating sustained therapeutic effect through stable transgene integration, such as CD19-directed CAR-T cell therapy for hematological malignancies. These transposon-based vectors enable robust gene transfer for cell engineering, but are fairly promiscuous with respect to where in the genome they insert their genetic cargo. On the contrary, R2-derived systems and CASTs represent promising technologies for programmable insertion, but are still under preclinical development. CRISPR-based PE provides a distinct route to precise sequence correction without double-strand breaks and is particularly attractive for the correction of monogenic disorders. Taken together, these technologies define a continuum from natural genome mobility to clinically relevant genome engineering. Continued optimization of delivery, targeting, and editing fidelity will determine how rapidly these approaches move from experimental innovation into routine clinical use.

PMID 42876085
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PubMedFrontiers in immunology2026-10-15

Case Report: Relapse of SLE associated with EBV infection in a patient after CAR-T cell therapy: a clinical case.

Zeng Ping P, Ren Qi Q, Gao Xianfei X, Xian Wei W et al.

We present the case of a 13-year-old boy with refractory systemic lupus erythematosus (SLE) who achieved drug-free remission after anti-CD19 CAR-T cell therapy, but subsequently experienced Epstein-Barr virus (EBV) reactivation on day 142 after CAR T-cell infusion and peak EBV load was 24,400 IU/mL with a severe drop in platelets to 8×109/L, which leading to relapse of SLE and manifestations of chronic active EBV disease (CAEBVD). The whole exogenous gene testing found X chromosome Xp22.33q28 region (chrX: 200855-155239820) a duplicate of about 155.04Mbp,which is associated with the development of Klinefelter syndrome (KS).The temporal association between EBV resurgence and SLE flare suggests that CAR-T-induced immunosuppression with some genetic background may permit EBV reactivation, which can be associated with the return of autoimmunity. This case highlights the need for vigilant monitoring for opportunistic infections and genetic background, particularly EBV, after CAR-T therapy for autoimmune diseases, as they may contribute to disease relapse.

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PubMedNature reviews. Rheumatology2026-10-15

Emerging therapies for knee osteoarthritis.

Courties Alice A, Winkler Tobias T, Conaghan Philip G PG, Berenbaum Francis F

Knee osteoarthritis (OA) is the most prevalent form of OA and a leading cause of chronic pain and disability worldwide. Its growing burden, driven mainly by ageing and obesity, is associated with major societal costs and increased cardiovascular mortality. Knee OA is now recognized as a heterogeneous whole-joint disease involving biomechanical, metabolic, inflammatory, osteochondral and neurovascular mechanisms. This complexity helps to explain why existing analgesics have modest efficacy and why disease-modifying OA drug development has repeatedly faltered. The therapeutic landscape is nevertheless evolving rapidly. Emerging symptomatic strategies include incretin-based therapies (semaglutide is the first to show substantial benefits for pain and function), neurotrophin modulation, extended-release intra-articular glucocorticoids, lubricating injectables and image-guided neurovascular interventions. In parallel, candidate disease-modifying OA drugs target cartilage anabolism, Wnt signalling, matrix-degrading enzymes, subchondral bone remodelling, immunometabolic pathways and local gene therapy. Several treatments, including locally administered GLP1 receptor agonists, the anabolic agent TPX-100 and intra-articular IL-1 receptor antagonist gene therapy, have shown encouraging signals, whereas mesenchymal stromal cell therapies have thus far demonstrated inconsistent efficacy across phase III clinical trials, highlighting the need for further standardization of mesenchymal stromal cell products and optimization of patient selection. Recent advances signal a shift towards a more diverse therapeutic landscape for knee OA, with emerging opportunities to target both symptoms and the underlying mechanisms of disease.

PMID 42875481
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PubMedMolecular genetics & genomic medicine2026-10-15

The First Case of Digenic MODY Diabetes Involving Compound Heterozygosity of Three Variants in the PDX1 and HNF1B Genes.

Płonka-Stępień Magdalena M, Szopa Magdalena M, Zawada Magdalena M, Malecki Maciej T MT

We report a rare case of digenic MODY. In 2016, at age 15, the patient was diagnosed with type 1 diabetes and began insulin therapy. After discrepancies in her glycaemic control were observed, an extensive differential diagnosis was conducted. In 2024, genetic testing confirmed monogenic diabetes, allowing for tailored treatment of the patient. The initial diagnosis was type 1 diabetes, later revised to MODY after Sanger screening. Genetic testing detected c.293C>T, p.Ala98Val in the HNF1A gene, which was initially misinterpreted as a variant causing Maturity Onset Diabetes of the Young (MODY), an autosomal dominant monogenic diabetes. Eventually, next-generation sequencing (NGS) revealed three heterozygous variants in the MODY genes: HNF1B and PDX1. The HNF1B and PDX1 genes are transcription factors responsible for pancreas development and insulin gene transcription. Two variants located very close to each other in the PDX1 gene were identified: c.694G>A, p.Gly232Ser and c.697G>T, p.Glu233Ter. The first causes an amino acid change, while the latter leads to an early termination codon. The third variant, c.827_828insT, p.Gly277ArgfsTer17, was found in the HNF1B gene, resulting in a premature STOP codon and a truncated nonsense protein product. This is the first report of a patient with a double MODY variant resulting in early protein termination. Overall, the available evidence suggests that all variants may be pathogenic. The variants' severity and likely digenic nature matched the proband's diabetes presentation, which didn't respond to oral agents and required insulin. Neither parent nor brother, each with a detected variant in a single gene, has developed diabetes. However, renal cysts were discovered in the mother and brother, and the father was diagnosed with prediabetes. This case highlights the severe presentation of likely digenic MODY, similar to type 1 diabetes. As NGS use increases, more patients like these are expected to be identified.

PMID 42876335
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PubMedNature medicine2026-10-15

Talazoparib plus enzalutamide in high-volume metastatic hormone-naive prostate cancer: a randomized phase 2 trial.

Zacchi Francesca F, Castro Elena E, Imbach Kathleen K, Rodriguez-Vida Alejo A et al.

Combining inhibition of poly(ADP-ribose) polymerase and androgen receptor (AR) pathway has demonstrated clinical activity in men with metastatic prostate cancer, although the extent of benefit in tumors lacking homologous recombination repair (HRR) gene alterations remains uncertain. We conducted a randomized phase 2 trial evaluating talazoparib plus enzalutamide versus enzalutamide alone in men with high-volume metastatic hormone-naive prostate cancer (mHNPC). Fifty-four patients starting androgen deprivation therapy received two cycles of enzalutamide lead-in before 1:2 randomization to enzalutamide (n = 17) or enzalutamide plus talazoparib (n = 37). The primary endpoint was met, with a 73% prostate-specific antigen (PSA) <0.2 ng ml-1 response rate at 12 months in the combination arm (95% confidence interval (CI) = 56-86%), exceeding the prespecified efficacy threshold (P < 0.001); the PSA <0.2 rate in the control arm was 64.7% (95% CI = 38-86%, P = 0.54 for exploratory comparison between arms). Grade ≥3 adverse events occurred in 68% patients receiving the combination versus 35% with enzalutamide alone, predominantly anemia (41%). Two fatal therapy-emergent myeloid neoplasms occurred in the enzalutamide plus talazoparib arm in patients with underlying genomic susceptibility. Analyses of paired tumor biopsies acquired at baseline and during enzalutamide lead-in phase demonstrated marked tumor transcriptional reprogramming after AR inhibition, including suppression of proliferation-associated and HRR-related gene expression programs, but without functional impairment of homologous recombination activity. Overall, talazoparib plus enzalutamide demonstrated clinical activity in patients with high-volume mHNPC but did not establish clear additional clinical benefit over enzalutamide alone in this biomarker-unselected population, while being associated with increased toxicity. ClinicalTrials.gov identifier: NCT04332744 .

PMID 42875559
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