Seprehvir (HSV1716) / Sorrento - LARVOL DELTA

Effect of type-2 diabetes medications and oncolytic viruses on mouse and human ovarian cancer cell lines (SITC 2025) - "Here we investigated the effect of several T2DM drugs (metformin, rosiglitazone, canagliflozin and sitagliptin) on mouse and human ovarian cancer cells in vitro, and the effect of this treatment on the activity of oncolytic DNA and RNA viruses: herpesvirus (HSV-1716) and reovirus (type 3 Dearing).Methods Mouse ID8 and BPPNM (p53−/−R172HBrca1−/−Pten−/−Nf1−/−MycOE), and human A2780 and SKOV3 ovarian cancer cells were treated with different concentrations of metformin, rosiglitazone, canagliflozin or sitagliptin in 2D and 3D environments and cell viability (monolayers) or spheroid size (3D cultures) tested at different times post-treatment (24-, 48- and 72-hours post-treatment)...Oncolytic virus activity on these cell lines was augmented in 2D environments only in the presence of metformin and sitagliptin, albeit the latter showed no effect on cell viability by itself. Interestingly, the drugs were also able to increase the capacity of the viruses to affect spheroid..."

Oncolytic virus • Preclinical • Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • NF1 • PTEN

Oncolytic virotherapy and tumor microenvironment modulation. (PubMed, Clin Exp Med) - "Among the most significant advancements, T-VEC, an FDA-approved herpesvirus, has been modified to express GM-CSF, enhancing immune activation in metastatic melanoma. Similarly, JX-594, a vaccinia virus, has been engineered for selective replication in tumor cells, demonstrating the potential of OVs to combine direct oncolysis with immune modulation. Other HSV-based OVs, such as HF10 and HSV1716, further highlight the ability of OVs to enhance immune cell infiltration and increase antigen presentation within the TME...Advances in viral engineering and immunomodulation hold the potential to revolutionize cancer treatment, offering more precise and effective therapeutic options. This review provides a comprehensive analysis of current progress in oncolytic virotherapy, emphasizing its potential to remodel the TME and improve clinical outcomes."

Biomarker • IO biomarker • Journal • Review • Immune Modulation • Immunology • Infectious Disease • Measles • Melanoma • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Tumor

Transforming Food Waste into Smart Nanoparticles: A Sustainable Approach to Drug Delivery (EACR 2025) - "Drugs included curcumin, resveratrol, 5-fluorouracil, epirubicin, and oncolytic viruses (HSV-1716, adenovirus). This study presents a sustainable, modular strategy for converting food waste into bioinspired nanoparticles for drug and virus delivery. The swirl mixer microfluidics platform significantly enhances scalability, reproducibility, and fabrication speed, offering a robust alternative to traditional systems. Valorisation of organic waste aligns with circular economy goals, and ongoing studies will evaluate in vivo therapeutic efficacy, biodistribution, and translational potential of this green nanomedicine approach."

Late-breaking abstract

Synergistic effects of herpes oncolytic virus and cyclophosphamide for recurrent malignant glioma: a narrative review. (PubMed, Ann Med Surg (Lond)) - "Oncolytic herpes viruses (oHSVs), particularly HSV1716, G207, and rQNestin34.5v, show promise in glioma treatment by selectively replicating in tumor cells. Preclinical and clinical studies demonstrate the safety and efficacy of oHSVs, with T-Vec being FDA-approved...CPA's immunomodulatory effects, suppressing regulatory T cells, improve oHSV efficiency. While obstacles remain, this synergistic approach offers hope for improved outcomes, necessitating further research and clinical validation."

IO biomarker • Journal • Oncolytic virus • Review • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

A phase I study of intratumoral/peritumoral herpes simplex virus-1 mutant HSV1716 in patients with refractory of recurrent high-grade gliomas: a Pediatric Brain Tumor Consortium Study (ISPNO 2024) - "We describe the administration of HSV1716 to two pediatric patients with recurrent high-grade glioma, without evidence of dose-limiting toxicity. Oncolytic viruses are currently being tested in pediatric patients in larger trials and in combinatorial trials in other tumor types. Despite the limited numbers, the data presented here will hopefully provide incremental steps toward improved immunovirotherapy of pediatric brain tumors."

Clinical • IO biomarker • P1 data • Brain Cancer • CNS Tumor • Diabetes • Glioma • Herpes Simplex • Oncology • Pediatrics • Solid Tumor

Oncolytic virotherapies for pediatric tumors. (PubMed, Expert Opin Biol Ther) - "We reviewed seven virus types that have been investigated in past or ongoing pediatric tumor clinical trials: adenovirus (AdV-tk, Celyvir, DNX-2401, VCN-01, Ad-TD-nsIL-12), herpes simplex virus (G207, HSV-1716), vaccinia (JX-594), reovirus (pelareorep), poliovirus (PVSRIPO), measles virus (MV-NIS), and Senecavirus A (SVV-001). However, the antitumor effects of OVT remain variable depending on tumor type and viral agent used. Although the widespread adoption of OVT faces many challenges, we are optimistic that OVT will play an important role alongside standard chemotherapy and radiotherapy for the treatment of malignant pediatric solid tumors in the future."

Journal • Oncolytic virus • Review • Herpes Simplex • Infectious Disease • Measles • Oncology • Pediatrics • Solid Tumor

HSV1716 Prevents Myeloma Cell Regrowth When Combined with Bortezomib In Vitro and Significantly Reduces Systemic Tumor Growth in Mouse Models. (PubMed, Viruses) - "Both murine models treated with HSV1716 had significantly lower tumor burden rates compared to the controls. In conclusion, HSV1716 has potent anti-myeloma effects and may represent a novel therapy for multiple myeloma."

Journal • Preclinical • Hematological Malignancies • Herpes Simplex • Multiple Myeloma • Oncology • ANXA5 • CASP8 • CASP9 • FASLG

Oncolytic herpesvirus therapy for mesothelioma: A phase I/IIa trial of intrapleural administration of HSV1716 (NCT01721018) (ESMO 2017) - P1/2; "The study demonstrated an acceptable safety profile of intra-pleural HSV1716 with evidence of viral replication and anti-tumour immunogenicity. This supports further studies in MPM, possibly involving combination with immune checkpoint inhibitors."

Adverse events • Checkpoint inhibition • Oncolytic virus • P1/2 data • Mesothelioma

"Great to see more Sheffield publications with HSV1716 @lawson_ma @MuthanaMunitta" (@sdanson1)

HSV1716 Infects Multiple Myeloma Cells and Leads to CD138 Downregulation (ASH 2022) - "While expression of ligands for activating NK cell receptors was not altered on infected versus uninfected RPMI8226 and MM1S cells, a strong downregulation of CD138 with maintained CD38 expression was observed upon HSV1716 infection. The implementation of oncolytic virotherapy as an immunotherapeutic platform for cancer treatment adds a new and promising therapeutic tool for combination therapies to the treatment options of MM."

IO biomarker • Hematological Disorders • Hematological Malignancies • Herpes Simplex • Infectious Disease • Multiple Myeloma • Oncology • CD38 • IFNG • LAMP1 • NCAM1 • NKG2D • SDC1

TRABECTEDIN ENHANCES ONCOLYTIC HERPES SIMPLEX VIROIMMUNOTHERAPY BY REDUCING BARRIERS TO VIRUS SPREAD AND IMMUNE EFFECTOR FUNCTION IN PRECLINICAL BONE SARCOMA MODELS (CTOS 2022) - "Our results indicate that trabectedin displays profound synergy with oncolytic herpes simplex viroimmunotherapy via multiple mechanisms including enhancement of virus infectivity, reduction of intratumoral immune-suppressive myeloid populations, and promotion of anti-tumor innate and adaptive immunity. Given that trabectedin is FDA-approved for human use and HSV1716 has shown clinical safety in pediatric patients, our findings should be readily translatable to the clinical setting where this combination therapy offers the potential to improve patient outcomes for those suffering from pediatric, adolescent and young adult bone sarcomas."

IO biomarker • Oncolytic virus • Preclinical • Ewing Sarcoma • Herpes Simplex • Infectious Disease • Oncology • Osteosarcoma • Pediatrics • Sarcoma • Solid Tumor

Inconsistencies in Modeling the Efficacy of the Oncolytic Virus HSV1716 Reveal Potential Predictive Biomarkers for Tolerability. (PubMed, Front Mol Biosci) - "By reporting these observations, we have potentially revealed a role for T-cell helper polarization in viral tolerability. Importantly, these findings were translated to human studies, whereby a Th1 cytokine profile was expressed in pleural effusions of patients that responded to HSV1716 treatment for malignant pleural mesothelioma with minimal side effects, warranting further investigation as a biomarker for predictive response."

Biomarker • IO biomarker • Journal • Oncolytic virus • Breast Cancer • Immune Modulation • Inflammation • Lung Cancer • Malignant Pleural Mesothelioma • Melanoma • Mesothelioma • Oncology • Respiratory Diseases • Solid Tumor

PTEN-L expressing HSV induces glioma stem cell differentiation and sensitizes glioblastoma to radiation in mice. (AACR 2022) - "Among all OVs, oncolytic Herpes Simplex Virus (oHSV) is substantially ahead in the clinic, with an oHSV T-VEC approved by the FDA for metastatic melanoma treatment...Further, several other oHSVs including G207 and HSV1716 are currently being tested for safety and efficacy against GBM...HSV-P10 infection in combination with irradiation reduces GSC tumor sphere formation in vitro and sensitizes GBMs to radiotherapy in an intracranial mouse xenograft model. Collectively, our findings provide a potential avenue to overcome GSC-mediated therapy resistance to improve the therapeutic efficacy for GBM patients."

Late-breaking abstract • Preclinical • Brain Cancer • Glioblastoma • Glioma • Melanoma • Oncology • Solid Tumor • CD133 • CD44 • GFAP • IL6 • NES • PTEN • SOX2

Nanobugs as Drugs: Bacterial Derived Nanomagnets Enhance Tumor Targeting and Oncolytic Activity of HSV-1 Virus. (PubMed, Small) - "Coassembling herpes simplex virus (HSV1716) with biocompatible magnetic nanoparticles derived from magnetotactic bacteria enables tumor targeting from circulation with magnetic guidance, protects the virus against neutralizing antibodies and thereby enhances viral replication within tumors. This approach additionally enhances the intratumoral recruitment of activated immune cells, promotes antitumor immunity and immune cell death, thereby inducing tumor shrinkage and increasing survival in a syngeneic mouse model of breast cancer by 50%. Exploiting the properties of such a nanocarrier, rather than tropism of the virus, for active tumor targeting offers an exciting, novel approach for enhancing the bioavailability and treatment efficacy of tumor immunotherapies for disseminated neoplasms."

Journal • Breast Cancer • Herpes Simplex • Oncology • Solid Tumor

[VIRTUAL] Breast cancer extracellular vesicles transfer immune cargo following oncolytic virotherapy (EACR 2021) - "Material and Methods The breast cancer cells lines MCF-7 and MDA-MB-231 were infected with the herpes simplex virus (HSV1716)...This will help identify the presence of immunological and viral cargo. Future studies will aim to investigate the antitumour properties of EVs of from infected cells."

IO biomarker • Oncolytic virus • Breast Cancer • Herpes Simplex • Immunology • Infectious Disease • Oncology • Solid Tumor • CD63 • CD9

[VIRTUAL] Breast cancer extracellular vesicles transfer immune cargo following oncolytic virotherapy (EACR 2021) - "Results and Discussions The breast cancer cells lines MCF-7 and MDA-MB-231 were infected with the herpes simplex virus (HSV1716)...This will help identify the presence of immunological and viral cargo. Future studies will aim to investigate the antitumour properties of EVs of from infected cells."

IO biomarker • Oncolytic virus • Breast Cancer • Herpes Simplex • Immunology • Infectious Disease • Oncology • Solid Tumor • CD63 • CD9

[VIRTUAL] Breast cancer extracellular vesicles transfer immune cargo following oncolytic virotherapy (EACR 2021) - "Results and Discussions The breast cancer cells lines MCF-7 and MDA-MB-231 were infected with the herpes simplex virus (HSV1716)...This will help identify the presence of immunological and viral cargo. Future studies will aim to investigate the antitumour properties of EVs of from infected cells."

IO biomarker • Oncolytic virus • Breast Cancer • Herpes Simplex • Immunology • Infectious Disease • Oncology • Solid Tumor • CD63 • CD9

[VIRTUAL] Breast cancer extracellular vesicles transfer immune cargo following oncolytic virotherapy (EACR 2021) - "Material and Methods The breast cancer cells lines MCF-7 and MDA-MB-231 were infected with the herpes simplex virus (HSV1716)...This will help identify the presence of immunological and viral cargo. Future studies will aim to investigate the antitumour properties of EVs of from infected cells."

IO biomarker • Oncolytic virus • Breast Cancer • Herpes Simplex • Immunology • Infectious Disease • Oncology • Solid Tumor • CD63 • CD9

[VIRTUAL] Breast cancer extracellular vesicles transfer immune cargo following oncolytic virotherapy (EACR 2021) - "Material and Methods The breast cancer cells lines MCF-7 and MDA-MB-231 were infected with the herpes simplex virus (HSV1716)...This will help identify the presence of immunological and viral cargo. Future studies will aim to investigate the antitumour properties of EVs of from infected cells."

IO biomarker • Oncolytic virus • Breast Cancer • Herpes Simplex • Immunology • Infectious Disease • Oncology • Solid Tumor • CD63 • CD9

[VIRTUAL] Breast cancer extracellular vesicles transfer immune cargo following oncolytic virotherapy (EACR 2021) - "Material and Methods The breast cancer cells lines MCF-7 and MDA-MB-231 were infected with the herpes simplex virus (HSV1716)...This will help identify the presence of immunological and viral cargo. Future studies will aim to investigate the antitumour properties of EVs of from infected cells."

IO biomarker • Oncolytic virus • Breast Cancer • Herpes Simplex • Immunology • Infectious Disease • Oncology • Solid Tumor • CD63 • CD9

[VIRTUAL] Breast cancer extracellular vesicles transfer immune cargo following oncolytic virotherapy (EACR 2021) - "Results and Discussions The breast cancer cells lines MCF-7 and MDA-MB-231 were infected with the herpes simplex virus (HSV1716)...This will help identify the presence of immunological and viral cargo. Future studies will aim to investigate the antitumour properties of EVs of from infected cells."

IO biomarker • Oncolytic virus • Breast Cancer • Herpes Simplex • Immunology • Infectious Disease • Oncology • Solid Tumor • CD63 • CD9

[VIRTUAL] Breast cancer extracellular vesicles transfer immune cargo following oncolytic virotherapy (EACR 2021) - "Results and Discussions The breast cancer cells lines MCF-7 and MDA-MB-231 were infected with the herpes simplex virus (HSV1716)...This will help identify the presence of immunological and viral cargo. Future studies will aim to investigate the antitumour properties of EVs of from infected cells."

IO biomarker • Oncolytic virus • Breast Cancer • Herpes Simplex • Immunology • Infectious Disease • Oncology • Solid Tumor • CD63 • CD9

Macrophages Mediate the Anti-Tumor Effects of the Oncolytic Virus HSV1716 in Mammary Tumors. (PubMed, Mol Cancer Ther) - "Finally, the anti-tumor effect of OV was markedly diminished when TAMs were depleted using clodronate liposomes. Together, our results show that TAMs play an essential role in support of the tumoricidal effect of the OV, HSV1716 - they both host viral replication via a novel, PCNA-dependent mechanism and are reprogramed to express a less immunosuppressive phenotype."

IO Biomarker • Journal • Oncolytic Virus • Breast Cancer • Herpes Simplex • Oncology • Solid Tumor • PCNA

Oncolytic herpesvirus therapy for mesothelioma - A phase I/IIa trial of intrapleural administration of HSV1716. (PubMed, Lung Cancer) - "Intrapleural HSV1716 was well-tolerated and demonstrated an anti-tumor immune response in MPM patients. These results provide a rationale for further studies with this agent in MPM and in combination with other therapies."

Journal • Oncolytic Virus • P1/2 data • Herpes Simplex • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Musculoskeletal Diseases • Oncology • Orthopedics • Solid Tumor

[VIRTUAL] Mutant BRAF small molecule inhibition enhances oncolytic herpes virus immunotherapy through increased immune cell recruitment and activation in melanoma (AACR-II 2020) - "Here, we show that the combination of PLX4720 (BRAFV600E inhibitor) and intratumoral oncolytic herpes virus HSV1716 led to a significant tumor reduction and improved survival over single-agent treatment in a murine BRAFV600E melanoma model. Using Tocky, we are identifying specific immune subsets that are stimulated following therapy and the real-time dynamics of antigen recognition and subsequent cell activation. These findings form the basis of future testing of drug-virus combinations in an effort to identify potent cytotoxic, as well as immuno-modulatory, strategies and their detailed mechanism of action."

IO Biomarker • Oncolytic Virus • Melanoma • Oncology • Solid Tumor • BRAF • CD8 • FOXP3 • PD-L1