Oncorine (recombinant human adenovirus type 5) / Mergen Ltd. - LARVOL DELTA

Case report: Local and systemic combination therapy: endoscopic injection of an oncolytic virus with PD-1 inhibitor for an elderly patient with advanced gastrointestinal cancer. (PubMed, Front Immunol) - "Subsequently, the patient was treated with an innovative regimen consisting of endoscopic intratumoral injections of Oncolytic adenovirus H101 in combination with the PD-1 inhibitor tislelizumab...The patient achieved nearly 4 months of progression-free survival and a substantial improvement in quality of life. This case highlights the potential of combining oncolytic virotherapy with PD-1 inhibition as a promising and novel personalized strategy for treating elderly patients with advanced gastrointestinal cancers who are unsuitable candidates for conventional therapies."

IO biomarker • Journal • Colorectal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CA 19-9 • CD4 • CD8

Intra-tumoral recombinant human adenovirus type 5 (H101) in persistent/recurrent/metastatic cervical cancer: Efficacy, safety, and mechanisms via spatial transcriptomics (ESMO-IO 2025) - "In responder stromal regions, proportions of epithelial cells, cancer-associated fibroblasts, and endothelial cells decreased, whereas myeloid cells, B cells, and T cells increased post-H101 injection.Conclusions Intra-tumoral H101-based therapy was effective and safe in P/R/M cervical cancer. Xenium profiling indicated that H101 reshaped and activated the TIME, and the therapeutic response may be associated with increased B cells and myeloid cells in the TIME.Legal entity responsible for the study The authors."

Clinical • Metastases • Cervical Cancer • Oncology • Solid Tumor

Overcoming immune resistance in advanced esophageal squamous cell carcinoma with recombinant human adenovirus type 5 by impacting the immune microenvironment: A case report (SITC 2025) - "The OVs could transiently suppress the tumor microenvironment during tumor cell lysis, potentially resulting in the temporary functional impairment of T cells and NK cells, consequently leading to a reduction in IFN-γ production.Conclusions Taken together, the intralymphatic injection of H101 combined with chemotherapy and immunotherapy may represent a promising clinical strategy for advanced ESCC patients with recurrent lymph node metastasis. Nevertheless, the efficacy and safety of H101 combination therapy in advanced ESCC needs to be validated through large-scale clinical trials in the future.Ethics Approval The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of the 900th Hospital of Joint Logistic Support Force (protocol code 2023-067).Consent A signed consent form was obtained from the patient, permitting the patient's data to be presented as a case report."

Case report • Clinical • IO biomarker • Metastases • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Squamous Cell Carcinoma • CD20 • CD4 • CD8 • IFNG • IL1B

Spatial transcriptomics unravels immune microenvironment reprogramming following H101 and anti-PD-1 combination therapy in PD-1 inhibitor-resistant melanoma (SITC 2025) - "Spatial transcriptomic dynamic monitoring revealed significant immune reprogramming in the TME following H101 treatment: CD3+/CD4+/CD8+ T cell infiltration increased 2.3-fold compared to baseline (p<0.001), with a notable increase in regulatory T cells (Tregs) that exhibited distinct transcriptional signatures from conventional suppressive Tregs, suggesting the existence of functionally reprogrammed subtypes; chemokines CXCL9 and CXCL10 expression were upregulated 4.2-fold and 3.8-fold, respectively, compared to pre-treatment levels (both p<0.001); CD68+ macrophage density increased 1.9-fold (p<0.01), however, classical M1/M2 polarization markers (iNOS, Arg1, IL-10) showed no significant changes, indicating that oncolytic virus induced a novel macrophage activation state.Conclusions This study systematically elucidates for the first time the unique immune reprogramming patterns induced by H101 combined with anti-PD-1 therapy through spatial transcriptomic..."

Combination therapy • IO biomarker • Melanoma • Oncology • Solid Tumor • CD4 • CD68 • CD8 • CXCL10 • CXCL9 • IL10

An Open-Label, Single-Arm Exploratory Clinical Study Evaluating the Efficacy and Safety of Intraperitoneal Perfusion of Recombinant Human Adenovirus Type 5 (H101) Combined with Tislelizumab, Platinum-Based, and Fluorouracil-Based Chemotherapy in the Treatment of Gastric Cancer with Peritoneal Metastasis (ChiCTR) - P=N/A | N=20 | Not yet recruiting | Sponsor: Renji Hospital ,Shanghai Jiaotong University School Of Medicine; Renji Hospital ,Shanghai Jiaotong University School Of Medicine

New trial • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

Recombinant human adenovirus type 5 (H101) combined with Anti-PD-1 therapy in advanced melanoma resistant to PD-1 inhibitors: Mechanistic insights from spatial tumor microenvironment analysis (ESMO 2025) - P=N/A | "Conclusions In conclusion, the spatial analysis of the immune microenvironment provides evidence for the activation of a systemic anti-tumor response by H101 combined with anti-PD-1 therapy. This combination therapy have been provide a new strategy for melanoma resistant to PD-1 inhibitors, thereby enabling precise patient selection to maximize therapeutic benefits."

Biomarker • IO biomarker • Metastases • Tumor microenvironment • Melanoma • Oncology • Solid Tumor

Recombinant human adenovirus type 5 (H101) combined with PD-1 inhibitors in patients with advanced solid tumors (ESMO 2025) - "These findings provided a strong rationale for the further clinical development of this combination therapy. Legal entity responsible for the study The authors."

Clinical • Metastases • Hepatocellular Cancer • Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Sarcoma • Solid Tumor

The combination treatment of oncolytic adenovirus H101 with transcatheter arterial embolization sequential thermal ablation for hepatocellular carcinoma: a retrospective study. (PubMed, Front Oncol) - "No patient experienced a serious adverse event, or a fatal or disabling event, due to the injection of oncolytic virus. This study suggests that HI01 combined with TAE sequential thermal ablation is both safe and effective for HCC, warranting further investigation through prospective randomized controlled trials."

Journal • Retrospective data • Hepatocellular Cancer • Oncology • Solid Tumor

Recombinant human adenovirus type 5 administration for the treatment of malignant ascites or pleural effusion in cancer patients: a meta-analysis. (PubMed, Front Oncol) - "The sensitivity analysis revealed high robustness of the results. H101 is effective and safe for the treatment of MA/MPE in patients with cancer and may be a promising modality for their clinical management."

Journal • Pleural effusion • Retrospective data • Review • Hematological Disorders • Leukopenia • Oncology • Respiratory Diseases

The combination treatment of oncolytic adenovirus H101 with transcatheter arterial embolization sequential thermal ablation for hepatocellular carcinoma: a retrospective study (Front Oncol) - "A total of 55 HCC patients were included....The median OS and PFS time were 77 and 12.3 months, respectively. The one-, two-, and three-year OS rates were 94.5%, 86.3%, and 77.3%, respectively. The PFS rates at one, two and three years were 56.4%, 26.3% and 20%, respectively."

Retrospective data • Hepatocellular Cancer

Oncolytic viruses in head and neck cancers: clinical applications and therapeutic potential. (PubMed, Front Microbiol) - "Talimogene laherparepvec (T-VEC) remains the only FDA-approved OV, while others like Oncorine and Teserpaturev show regional efficacy. Oncolytic virotherapy holds considerable promise in HNSCC. Advances in virus design, delivery platforms, and personalized approaches are essential for transitioning this modality from experimental settings into routine clinical practice."

Journal • Review • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

PTCA199-8: Oncolytic Virus Plus PD-1 Inhibitor to Patients With Advanced Pancreatic Cancer (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Fudan University | Trial primary completion date: Jan 2026 ➔ Jan 2028

Trial primary completion date • Oncology • Pancreatic Cancer • Solid Tumor

Phase II, open label, single center clinical study of oncolytic adenovirus H101 combined with PD-1 inhibitor for metastatic castration resistant prostate cancer that has failed standard treatment (ChiCTR) - P2 | N=25 | Not yet recruiting | Sponsor: Zhejiang Cancer Hospital; Zhejiang Cancer Hospital

New P2 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Induction of abscopal effect combining H101 oncolytic virotherapy with tislelizumab in a patient with advanced hepatocellular carcinoma: a case report. (PubMed, Am J Cancer Res) - "Rapid tumor shrinkage was associated with severe local inflammation and a reduction in peripheral white blood cell counts. These findings suggest that oncolytic virotherapy may elicit an abscopal effect by activating and recruiting immune cells into the tumor microenvironment."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CD4

Overcoming immune resistance in advanced esophageal squamous cell carcinoma with recombinant human adenovirus type 5 by impacting the immune microenvironment: a case report. (PubMed, Front Immunol) - "We also observed significant increases in the expression of CD3, CD4, CD8, CD20 and IL-1β after two relapsed H101 treatments based on multiplex immunofluorescence analysis. Intralymphatic injection of H101 combined with chemotherapy and immunotherapy may represent a promising clinical strategy for advanced ESCC patients with recurrent lymph node metastasis."

IO biomarker • Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Hepatocellular Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD20 • CD4 • CD8 • IL1B

Recombinant human adenovirus type 5 (H101) combined with anti-PD-1 monoclonal antibody in the treatment of patients with advanced melanoma with previous immunotherapy failure: A single-site, single-arm, prospective study. (ASCO 2025) - P=N/A | "The data showed that the combination of recombinant human adenovirus 5 injection plus Toripalimab demonstrated acceptable toxicity and promising antitumor efficacy in patients with advanced and refractory melanoma. Mechanistically, therapeutic response was directly regulated via specific mono/macro populations at tumor-immune boundary that may directly involve T cell recruitment and tumor killing."

Clinical • IO biomarker • Metastases • Anemia • Cardiovascular • Cutaneous Melanoma • Hematological Disorders • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor

Talimogene Laherparepvec (T-VEC): Expanding Horizons in Oncolytic Viral Therapy Across Multiple Cancer Types. (PubMed, Anticancer Agents Med Chem) - "By exploring recent trials, such as T-VEC with neoadjuvant chemotherapy in triple-negative breast cancer and pembrolizumab in HNSCC, highlighting its versatility. Comparative analysis with other oncolytic viruses like HF-10, oncorine (H101), and measles virus variants positions T-VEC within the virotherapy landscape. Key challenges-systemic delivery, immune clearance, and biomarker development for patient selection-are addressed alongside strategies to enhance immune modulation through novel combinations. This review underscores T-VEC's expanding role in cancer treatment, offering clinicians' and researchers' insights to optimize its therapeutic horizons across diverse malignancies."

IO biomarker • Journal • Breast Cancer • Head and Neck Cancer • Herpes Simplex • Immune Modulation • Immunology • Infectious Disease • Measles • Melanoma • Non-melanoma Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • CSF2

Oncolytic Virus H101 Combined With Lenvatinib Plus Toripalimab Compared With FOLFOX in Patients With Advanced Biliary Tract Cancer (OPTIONS-06) (clinicaltrials.gov) - P2 | N=74 | Not yet recruiting | Sponsor: Fudan University

New P2 trial • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor

Oncolytic adenovirus H101 enhances the anti-tumor effects of PD-1 blockade via CD47 downregulation in tumor cells. (PubMed, Oncol Res) - "To investigate the anti-tumor effects of an E1B55KD-deleted oncolytic adenovirus, H101, in combination with a humanized anti-PD-1 (Programmed cell death protein 1) monoclonal antibody, Camrelizumab...These results suggested that H101 may act synergistically to enhance the therapeutic efficacy of PD-1 blockade in cancer via suppressing CD47 signaling, which may promote macrophages to phagocytose tumor cells and activate CD8+ T cells. The combination of H101 with PD-1 blockade exhibits potential as a novel strategy for the treatment of cancer."

IO biomarker • Journal • Bladder Cancer • Brain Cancer • CNS Tumor • Genito-urinary Cancer • Glioblastoma • Infectious Disease • Oncology • Solid Tumor • CD47 • CD8 • IFNG • IL12A • IL2RG • PD-L1 • PRKDC

Enhancing pancreatic cancer treatment: the role of H101 oncolytic virus in irreversible electroporation. (PubMed, Front Immunol) - "This combination boosts therapeutic effectiveness by activating the JNK-MAPK pathway and promoting tumor cell apoptosis. These findings suggest that the H101 oncolytic virus could serve as a valuable adjunct to improve the efficacy of IRE treatment."

Journal • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Oncolytic Virotherapy Plus PD-1 Inhibitor and Lenvatinib for Patients with Advanced Pancreatic Cancer (clinicaltrials.gov) - P1 | N=56 | Completed | Sponsor: Fudan University | Recruiting ➔ Completed | Phase classification: P1b ➔ P1 | N=25 ➔ 56 | Trial completion date: Mar 2025 ➔ Apr 2024 | Trial primary completion date: Mar 2025 ➔ Apr 2024

Enrollment change • Phase classification • Trial completion • Trial completion date • Trial primary completion date • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Reverse resistance to immune checkpoint inhibitor in a patient with recurrent cardia cancer by intratumoral injection of recombinant human adenovirus type 5: a case report and literature review. (PubMed, Front Oncol) - "We also observed a significant increase of infiltrated CD4+T cells in biopsy tissues after H101 treatment. Our study not only conformed the value of oncolytic viruses to reverse ICI resistance in patients with gastric cancer, but also revealed its underlying impact on immune microenvironment."

Checkpoint inhibition • Journal • Review • Gastric Cancer • Oncology • Pain • Solid Tumor • CD4

Sequential T and I With H101 Via HAI for BCLC C Stage HCC: A Prospective Single-Center Single-Arm Pilot Study (clinicaltrials.gov) - P2 | N=11 | Not yet recruiting | Sponsor: Henan Cancer Hospital

New P2 trial • Hepatocellular Cancer • Oncology • Solid Tumor

Breaking Barriers: Animal viruses as oncolytic and immunotherapeutic agents for human cancers. (PubMed, Virology) - "Notably, four leading contenders in this domain, Rigvir® in Latvia, T-VEC in the United States, H101 in China and Teserpaturev (DELYTACT®) in Japan, have earned approval for treating metastatic melanoma (Rigvir and T-VEC), nasopharyngeal carcinoma and malignant glioma, respectively...Furthermore, we provide a thorough examination of animal-derived oncolytic viruses, highlighting their respective strengths and limitations. Lastly, we explore the promising potential of leveraging animal viruses as potent oncolytic agents, offering new avenues for enhancing the efficacy and reach of human cancer therapeutics."

Journal • Review • Brain Cancer • CNS Tumor • Glioma • Melanoma • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

Recombinant human adenovirus type 5 promotes anti-tumor immunity via inducing pyroptosis in tumor endothelial cells. (PubMed, Acta Pharmacol Sin) - "Furthermore, we showed that the combination of H101 with the immune checkpoint inhibitor PD-L1 antibody (10 mg/kg, i.p., every three days for three times) exerted synergic suppression on B16F10 tumor growth in the mice. This study demonstrates that, in addition to oncolysis, H101 inhibits melanoma growth by promoting anti-tumor immunity and inducing pyroptosis of vascular endothelial cells."

Journal • Melanoma • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • CASP1 • CD8