北京若生智能科技有限公司
Drug Database
HS

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

✓ Approved

Megapharm Ltd · POLA1 · 细胞治疗

什么是 HSV-tk gene therapy？

HSV-tk gene therapy 是一种细胞治疗，由Megapharm Ltd研发。该药已获批，用于治疗相关适应症，给药途径：Injectable (Others)、Intravenous (IV)。

药物档案

商品名HSVtk, Zalmoxis, TK therapy
公司Megapharm Ltd
药物类别细胞治疗, 基因治疗
分子靶点POLA1
给药途径Injectable (Others), Intravenous (IV)
状态Approved
来源： ClinicalTrials.gov, Megapharm Ltd

作用机制

分子靶点

HSV-tk gene therapy 作用于 1 个分子靶点：

POLA1DNA polymerase alpha 1, catalytic subunit (PDR, POLA)
需要更深入的分析？Noah AI 可解释复杂机制并与同类药物比较。

治疗适应症

HSV-tk gene therapy 针对 1 个适应症，涉及 1 个治疗领域。

治疗领域疾病/病症分期
Immune system disordersChronic graft versus host disease✓ Approved

相关研究文献

PubMedClinical and translational medicine2026-09-11

Bevacizumab plus nab-paclitaxel and platinum as second-line therapy for driver-gene-negative non-squamous non-small cell lung cancer after immunochemotherapy: A prospective single-arm single-centre study.

Lin Ying Y, Yu Yunbo Y, Hu Zhihuang Z, Wei Chenchen C et al.

Effective second-line therapy is urgently needed for patients with driver-gene-negative non-squamous non-small cell lung cancer (nsqNSCLC) who progress after first-line immunochemotherapy. This study aims to evaluate the efficacy and safety of bevacizumab combined with nab-paclitaxel and platinum (the BAP regimen) in this setting. This prospective, single-arm, single-centre study enrolled 56 patients with advanced driver-gene-negative nsqNSCLC failing first-line immunochemotherapy. Patients received bevacizumab, nab-paclitaxel, and platinum (carboplatin or cisplatin) for 4-6 cycles, followed by bevacizumab maintenance. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. All patients had failed first-line platinum-based immunochemotherapy. The confirmed ORR was 46.4% (26/56, 95% confidence interval [CI]: 34.0%-59.3%, p < 0.001), and DCR was 75%. The median PFS and OS were 5.6 (95% CI: 4.35-6.79) and 18.8 (95% CI: 10.31-27.24) months. Patients with ≤ 2 metastatic organs had a significantly longer median PFS than those with >2 metastatic organs (p = 0.014). Multivariable Cox analysis showed that a platinum-free interval <6 months was an independent biomarker of worse PFS. The safety profile was manageable. Plasma proteomics identified baseline high TWEAK level as a potential biomarker for response to both the second-line BAP regimen and first-line immunochemotherapy. Patients with high baseline TWEAK levels before first-line immunochemotherapy showed a median OS of 39.8 months under this sequential treatment modality. The BAP regimen demonstrated preliminary efficacy with manageable safety as a second-line therapy for patients with advanced driver-gene-negative nsqNSCLC after immunochemotherapy. Plasma TWEAK levels may serve as a potential biomarker to help identify patients who might benefit most from this sequential treatment modality, pending further independent validation. Further studies are needed.

PMID 42723577
阅读全文 →
PubMedTranslational lung cancer research2026-09-11

Identification of candidate variants in plasma associated with early versus late disease progression under anti-PD-1 therapy in metastatic NSCLC.

Rodriguez-Casanova Aitor A, Mondelo-Macía Patricia P, Leon-Mateos Luis L, García-González Jorge J et al.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death protein 1 (anti-PD-1) antibodies, have significantly improved outcomes in patients with metastatic non-small cell lung cancer (mNSCLC). However, substantial heterogeneity exists in clinical benefit, with some patients exhibiting early progression (EP) and others late progression (LP). To date, no biomarkers of EP versus LP disease have been implemented in clinical practice. Circulating tumor DNA (ctDNA) analysis represents a minimally invasive strategy for identifying such biomarkers. In this proof-of-concept study, we evaluated the performance of the TruSight Oncology 500 ctDNA (TSO500 ctDNA) panel and explored its feasibility to identify candidate variants associated with early and late disease progression under anti-PD-1 therapy. Baseline ctDNA from eight mNSCLC patients treated with pembrolizumab was extracted and sequenced using the TSO500 ctDNA assay, a 523-gene targeted next-generation sequencing panel. Patients were classified according to their response as LP or EP. Variant calling was performed using the DRAGEN Bio-IT platform, and variants were annotated and clinically interpreted using the Clinical Genomics Workspace (CGW; PierianDx) according to Association for Molecular Pathology (AMP)/American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. Survival outcomes were assessed using Kaplan-Meier and log-rank tests. Performance of ctDNA variants was evaluated using receiver operating characteristic (ROC) curve analysis, and multi-gene models were assessed using leave-one-out cross-validation with penalized logistic regression. All patients harbored detectable variants, including SNVs (100%), MNVs (87.5%), deletions (75%), and insertions (62.5%). Tier I variants were identified in 37.5% of patients, while all cases showed tier II and multiple tier III alterations. TP53 variants were associated with poorer outcomes under anti-PD-1 therapy. Individual gene alterations in TP53, ERBB3, SMC1A or LATS1 showed moderate discriminatory performance between LP and EP patients; however, combination of mutated genes improved apparent discrimination. Notably, specific two-gene combinations (SMC1A + LATS1 or ERBB3 + LATS1) showed the highest discriminatory performance between LP and EP patients in this exploratory cohort. This study demonstrates the feasibility and analytical performance of the TSO500 ctDNA panel and provides hypothesis-generating evidence that plasma gene variants may be useful to evaluate early versus late disease progression in patients with mNSCLC receiving immunotherapy.

PMID 42723788
阅读全文 →
PubMedGan to kagaku ryoho. Cancer & chemotherapy2026-09-11

[Perioperative Immune Checkpoint Inhibitor Therapy for Non-Small Cell Lung Cancer].

Matsuda Suguru S, Kenmotsu Hirotsugu H

Surgery is an important treatment for resectable non-small cell lung cancer (NSCLC). However, some patients experience the recurrence even after complete resection, and perioperative systemic therapy can improve treatment outcomes for patients receiving surgery. In recent years, immune checkpoint inhibitors (ICIs) have been a standard treatment in addition to platinum-based chemotherapy for those patients, and perioperative chemotherapy plus ICI have shown improvements of pathological response or event-free survival, with overall survival benefits in some trials. However, these data of treatment benefits are different among patients with each stage, driver gene alterations, or PD-L1 expression. Assessment of molecular residual disease (MRD) using circulating tumor DNA (ctDNA) has been reported to be associated with pathological response or prognosis, although further prospective validation is needed. ICIs have become an important component of perioperative treatment for patients with resectable NSCLC.

PMID 42723234
阅读全文 →
PubMedFrontiers in aging2026-09-11

Grip strength as a systems biomarker of aging: neuromuscular junction constraints and biomarker decoupling in gene therapy.

Sewell Patrick E PE, Jensen Christopher C

Grip strength has emerged as one of the most robust predictors of mortality, disability and healthspan across populations. Yet its predictive validity rests on an often-unstated assumption: that grip strength serves as a passive readout of systemic biological integrity rather than an isolated measure of forearm function. Here we propose that grip strength derives its prognostic power from its position as a convergent output of multiple aging-sensitive physiological systems-including neuromuscular, vascular, metabolic, endocrine and inflammatory networks. We highlight the neuromuscular junction (NMJ) as a particularly critical and often-overlooked rate-limiting factor, noting that age-related strength loss (∼2.5-4% annually) outpaces mass loss (∼0.6-1% annually) by two-to fivefold-a disparity attributable in large part to NMJ deterioration. We introduce the concept of biomarker decoupling and apply it to the emerging landscape of longevity gene therapies being explored in early translational and compassionate-use settings-including follistatin, klotho, FOXO3, hTERT, SIRT1, PGC-1α, VEGF and FGF21. Critically, we argue that follistatin's anabolic efficacy is contingent on intact NMJ integrity, with denervated muscle fibers exhibiting a blunted net anabolic response despite elevated follistatin expression-creating a therapeutic paradox wherein mass gains can occur without proportional functional improvement. We provide a conceptual analysis of how each therapy may influence grip strength, predict decoupling risk based on the breadth of systems affected, outline plausible timing windows for intervention, and propose a heuristic framework for clinical interpretation. The decoupling categories and any numeric ranges presented here are conceptual and hypothesis-generating rather than empirically validated.

PMID 42723927
阅读全文 →
PubMedFrontiers in medicine2026-09-11

RBPMS::NTRK3-rearranged sacral malignant spindle cell tumor in neurofibromatosis diagnosed by RNA sequencing: a case report and literature review.

Chen Chaopeng C, Qi Bin B, Miao Yuanyuan Y, Zhuang Zhujiang Z et al.

Malignant spindle cell tumors arising in patients with neurofibromatosis are diagnostically challenging because malignant peripheral nerve sheath tumor (MPNST) and emerging NTRK-rearranged mesenchymal neoplasms may show overlapping clinical, histological, and immunophenotypic features. We report a 31-year-old man with a more than 20-year history of neurofibromatosis who presented with progressive lumbosacral pain and left lower-limb numbness. Imaging revealed a large cystic-solid sacral mass involving the S1-S2 region and extending through the sacral foramina into the pelvis. Core needle biopsy showed an intermediate-grade malignant spindle cell tumor with partial CD34 expression, strong pan-TRK positivity, increased p53 expression, and a Ki-67 labeling index up to 50% in hotspot areas. NTRK1 break-apart fluorescence in situ hybridization (FISH) was negative; however, RNA-based next-generation sequencing identified an RBPMS::NTRK3 fusion, establishing a molecularly confirmed NTRK3-rearranged spindle cell neoplasm and explaining the pan-TRK positivity as a true-positive result. The negative NTRK1 FISH reflected involvement of NTRK3 rather than NTRK1, illustrating that single-gene FISH cannot exclude an NTRK fusion. Given the large local tumor burden, neurological symptoms, high surgical morbidity, and the confirmed actionable fusion, the patient received molecularly guided entrectinib combined with palliative radiotherapy, with marked pain relief, neurological improvement, and radiological tumor shrinkage; at the most recent follow-up, approximately 7 months after starting entrectinib, he remained without evidence of disease progression. This case underscores that pan-TRK positivity should prompt confirmatory RNA-based sequencing rather than reliance on single-gene FISH; that actionable NTRK fusions may occur in the neurofibromatosis setting, where MPNST is the principal differential; and that molecularly informed multimodal therapy can benefit anatomically complex tumors, although response attribution requires caution when targeted therapy and radiotherapy are combined.

PMID 42724224
阅读全文 →
PubMedCancer pathogenesis and therapy2026-09-11

An immune exhaustion signature predicts prognosis and identifies patients with diffuse large B-cell lymphoma (DLBCL) who derive preferential benefit from chimeric antigen receptor (CAR)-T cell therapy.

Zheng Bo B, Hu Wanqian W, Fang Ying Y, Li Rong R

The tumor microenvironment (TME) is a key determinant of prognosis in diffuse large B-cell lymphoma (DLBCL). While T-cell exhaustion is implicated in therapeutic failure, its precise molecular hallmarks and utility for predicting response to modern immunotherapies, such as chimeric antigen receptor (CAR)-T cell therapy, remain unclear. We performed an integrative analysis of transcriptomic and clinical data from multiple DLBCL cohorts (The Cancer Genome Atlas [TCGA], GSE181063, GSE10846, GSE248835, GSE182434). We used unsupervised clustering, exploratory analysis of single-cell RNA sequencing data, and the least absolute shrinkage and selection operator for variable selection (LASSO-Cox) regression to characterize the exhausted TME, construct a prognostic model, and evaluate its predictive value for CAR-T cell therapy. The model's dynamic behavior was assessed in a proof-of-concept longitudinal cohort of patients treated with the T-cell-engaging bispecific antibody glofitamab. We identified a "high-exhaustion" subtype associated with significantly poorer overall survival (OS; log-rank P = 0.016). Based on this, we developed a five-gene immune exhaustion-Related Prognostic Score (IERPS) that served as a robust independent predictor of poor OS across multiple cohorts. Critically, in a cohort of 256 relapsed/refractory patients, the IERPS was strongly prognostic for event-free survival (EFS) in the standard-of-care (SOC) arm (HR = 2.02, 95% confidence interval [95% CI]: 1.07-3.81, P = 0.029) but lost prognostic significance in the CAR-T arm (HR = 0.70, 95 % CI: 0.35-1.40, P = 0.314). This significant interaction suggests that CAR-T cell therapy may abrogate the poor prognosis associated with a high IERPS. Biologically, exploratory single-cell analysis (n = 4 samples) defined the high-IERPS state by hallmarks of classical T-cell exhaustion, and a descriptive case study showed the score dynamically tracked clinical response to glofitamab. A state of active T-cell exhaustion and a suppressive TME drive the adverse immune phenotype in DLBCL. Our IERPS model captures this dysfunctional state, acting as a powerful prognostic tool and, more importantly, as a potential predictive biomarker to identify high-risk patients who appear to overcome their inherently poor prognosis through CAR-T cell therapy.

PMID 42724625
阅读全文 →

注册免费账户还可查看另外 9996 篇文献

免费注册查看全部文献 →

了解更多HSV-tk gene therapy