ParvOryx (parvovirus H-1) / Oryx - LARVOL DELTA

Mapping the sialic acid-binding sites of LuIII and H-1 parvovirus. (PubMed, J Virol) - "This study investigates the structures of LuIII and H-1PV in the presence of their glycan receptors to identify and map the capsid loci that are responsible for this interaction. This knowledge may aid future capsid engineering to improve oncolytic targeting efficiency."

Journal • Infectious Disease • Oncology

H-1 Parvovirus-Induced Oncolysis and Tumor Microenvironment Immune Modulation in a Novel Heterotypic Spheroid Model of Cutaneous T-Cell Lymphoma. (PubMed, Cancers (Basel)) - "In CTCL spheroid co-cultures with PBMCs, increased spheroid infiltration with immune cells was detected upon co-culture treatment with the virus. In conclusion, our preclinical data show that H-1PV may hold significant potential as an ingenious viroimmunotherapeutic drug candidate against CTCL."

Biomarker • IO biomarker • Journal • Tumor microenvironment • Cutaneous T-cell Lymphoma • Hematological Disorders • Hematological Malignancies • Immune Modulation • Immunology • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • BCL2

Biomarker screen for efficacy of oncolytic virotherapy in patient-derived pancreatic cancer cultures. (PubMed, EBioMedicine) - "Considering the heterogeneity of PDAC and the complexity of biological therapies such as OVs, no single biomarker can explain the spectrum of response patterns. For selection of a particular OV, PDAC molecular subtype, ISG expression as well as activation of distinct signaling and metabolic pathways should be considered. Combination therapies can overcome resistance in specific constellations. Overall, oncolytic virotherapy is a viable treatment option for PDAC, which warrants further development. This study highlights the need for personalised treatment in OVT. By providing all primary data, this study provides a rich source and guidance for ongoing developments."

IO biomarker • Journal • Oncolytic virus • Gastrointestinal Cancer • Hepatology • Infectious Disease • Measles • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CGAS • LGALS1

Pattern of tumor regression of recurrent glioblastoma after intratumoral virus injection of oncolytic parvovirus H-1 strongly supports virus contribution in effective viro-immunotherapy (CIMT 2024) - "Upon request and based on a compassionate use agreement, a group of unselected patients with recurrent GBM were treated with H-1PV in combination with immunotherapy using Bevacizumab and PD-1 blockade with Nivolumab or Pembrolizumab. Interestingly, in patient 2 adjacent tumor areas not covered by local injection had no morphological changes on MRI and were slowly progressing. In conclusion, while clinical data with a high ORR under triple H-1PV based viro-immunotherapy indicated a strong additional effect of the virus, the co-localization of intratumoral virus inoculum and tissue destruction adds further compelling evidence."

IO biomarker • Oncolytic virus • Tumor mutational burden • Brain Cancer • CNS Tumor • Glioblastoma • Infectious Disease • Oncology • Solid Tumor • TMB

Pattern of tumor regression of recurrent glioblastoma after intratumoral virus injection of oncolytic parvovirus H-1 strongly supports virus contribution in effective viro-immunotherapy (CIMT 2024) - "Upon request and based on a compassionate use agreement, a group of unselected patients with recurrent GBM were treated with H-1PV in combination with immunotherapy using Bevacizumab and PD-1 blockade with Nivolumab or Pembrolizumab. Interestingly, in patient 2 adjacent tumor areas not covered by local injection had no morphological changes on MRI and were slowly progressing. In conclusion, while clinical data with a high ORR under triple H-1PV based viro-immunotherapy indicated a strong additional effect of the virus, the co-localization of intratumoral virus inoculum and tissue destruction adds further compelling evidence."

IO biomarker • Oncolytic virus • Tumor mutational burden • Brain Cancer • CNS Tumor • Glioblastoma • Infectious Disease • Oncology • Solid Tumor • TMB

The Complex Role of Infectious Agents in Human Cutaneous T-Cell Lymphoma Pathogenesis: From Candidate Etiological Factors to Potential Therapeutics. (PubMed, Pathogens) - "The complexity and multifacetedness of the Parvoviridae family of viruses are illustrated by presenting another protoparvovirus, the rat H-1 parvovirus (H-1PV). H-1PV belongs to the same genus as the CutaV but carries considerable potential for therapeutic applications in cutaneous lymphoma."

Journal • Review • Cutaneous T-cell Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Stability and safety key factors of the oncolytic protoparvovirus H-1 from manufacturing to human application. (PubMed, Appl Microbiol Biotechnol) - "• H-1PV is stable during in-use and does not adsorb to injection devices during patient administration. • Hygiene plan for H-1PV with physicochemical methods has been established."

Journal • Oncolytic virus • Brain Cancer • CNS Tumor • Gastrointestinal Cancer • Glioblastoma • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Oncolytic Rodent Protoparvoviruses Evade a TLR- and RLR-Independent Antiviral Response in Transformed Cells. (PubMed, Pathogens) - "The oncolytic rodent protoparvoviruses (PVs) minute virus of mice (MVMp) and H-1 parvovirus (H-1PV) are promising cancer viro-immunotherapy candidates capable of both exhibiting direct oncolytic activities and inducing anticancer immune responses (AIRs)...This virus-triggered evasion mechanism involves a viral factor(s), which exert(s) an inhibitory action on IFN production, particularly in transformed/tumor cells. These findings pave the way for the development of second-generation PVs that are defective in this evasion mechanism and therefore endowed with increased immunostimulatory potential through their ability to induce IFN production in infected tumor cells."

Journal • Preclinical • Infectious Disease • Oncology

HIGH RATE OF OBJECTIVE: ANTI-TUMOR RESPONSE IN 9 PATIENTS WITH GLIOBLASTOMA AFTER VIRO-IMMUNOTHERAPY WITH ONCOLYTIC PARVOVIRUS H-1 IN COMBINATION WITH BEVACICUMAB AND PD-1 CHECKPOINT BLOCKADE (SNO 2018) - "H-1PV based viro-immunotherapy lead to ORR in 78% of glioblastoma patients. This is a much higher response rate than reported for treatment with either bevacizumab or checkpoint blockade and it supports further systematic clinical development of this novel concept for malignant glioma therapy."

Checkpoint inhibition • Clinical • Combination therapy • IO biomarker • Oncolytic virus • PD(L)-1 Biomarker • Brain Cancer • Oncology • Solid Tumor

Design and Characterization of Mutated Variants of the Oncotoxic Parvoviral Protein NS1. (PubMed, Viruses) - "Oncotoxic proteins such as the non-structural protein 1 (NS1), a constituent of the rodent parvovirus H1 (H1-PV), offer a novel approach for treatment of tumors that are refractory to other treatments...Expression of NS1 variants had no effect on cell viability in NS1 unresponsive control HepG2 cells or primary mouse hepatocytes. The availability of new NS1 variants in combination with a better understanding of their modes of action offers new possibilities for the design of innovative cancer treatment strategies."

Journal • Gastrointestinal Cancer • Gene Therapies • Hepatocellular Cancer • Hepatology • Infectious Disease • Oncology • Solid Tumor

Oncolytic H-1 Parvovirus Hijacks Galectin-1 to Enter Cancer Cells. (PubMed, Viruses) - "Strikingly, the addition of purified galectin-1 sensitises poorly susceptible GBM cell lines to H-1PV killing activity by rescuing cell entry. Together, these findings demonstrate that galectin-1 is a crucial determinant of the H-1PV life cycle."

Journal • Oncolytic virus • Brain Cancer • Gastrointestinal Cancer • Glioblastoma • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • LGALS1

Oncolytic H-1 Parvovirus in Combination with Pro-Apoptotic Drug ABT-737, Shows Improved Cytotoxicity and Immune Activation in Prostate Cancer Cells (ASGCT 2022) - "H-1 Parvovirus (H-1PV) is one such “clinically relevant” OV, which has been extensively studied in various cancer models and evaluated in phase I/II clinical trials for the treatment of patients with glioblastoma multiforme and pancreatic ductal adenocarcinoma. Furthermore, we see peripheral activation of T-cells through the upregulation of early activation marker CD69. The combination also shows an improved activation of natural killer cells through an increase in degranulation marker CD107a and intracellular IFN"

Combination therapy • IO biomarker • Oncolytic virus • Brain Cancer • Genito-urinary Cancer • Glioblastoma • Immune Modulation • Immunology • Inflammation • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Prostate Cancer • Solid Tumor • CALR • CD69 • CD86 • LAMP1

Identification of an Antiviral Drug as a Novel Potentiator of H-1PV-Mediated Oncolysis (ASGCT 2022) - "We are currently validating these pathways by independent methods, as well as investigating the effect of ledipasvir on H-1PV replication. Our data demonstrates for the first time that ledipasvir is able to potentiate the oncotoxicity of H-1PV and is a promising candidate for combination therapy in the clinics."

Brain Cancer • Breast Cancer • Glioblastoma • Glioma • Hematological Malignancies • Hepatology • Infectious Disease • Inflammation • Leukemia • Lung Cancer • Lymphoma • Oncology • Ovarian Cancer • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Phase 2 trial of oncolytic H-1 parvovirus therapy shows safety and immune cell activity in patients with metastatic pancreatic ductal adenocarcinoma. (PubMed, Clin Cancer Res) - "The trial met all primary objectives, revealed no environmental risks and indicated favorable immune modulation after administration of ParvOryx. It can be considered a good basis for further systematic clinical development alone or in combination with immunomodulatory compounds."

Clinical • Journal • Oncolytic virus • P2 data • Immune Modulation • Immunology • Inflammation • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Generation and Validation of Monoclonal Antibodies Suitable for Detecting and Monitoring Parvovirus Infections. (PubMed, Pathogens) - "In addition to mAbs detecting the NS1 of parvovirus H-1 (H-1PV) (belonging to the Rodent protoparvovirus 1 species, which is currently under validation as an anti-cancer agent), we generated tools with which to monitor infections by human cutavirus (CuV) and B19 virus (B19V) (belonging to the Primate protoparvovirus 3 and the Primate erythroparvovirus 1 species, respectively, which were both found to persistently infect human tissues). As well as mAbs able to detect NS1 from a broad range of parvoviruses, we obtained entities specific for either (distinct) members of the Rodent protoparvovirus 1 species, human CuV, or human B19V."

Journal • Infectious Disease • Oncology

Upstream process optimization and micro- and macrocarrier screening for large-scale production of the oncolytic H-1 protoparvovirus. (PubMed, Appl Microbiol Biotechnol) - "• We screened carriers for cell growth, bead-to-bead transfer capability, and H-1PV yield. • High virus yield is achieved with Cytodex® 1 and macrocarrier for iCellis® in Erlenmeyer flasks."

Journal • Oncology

[VIRTUAL] Directed evolution generates novel oncolytic H1 parvoviruses with improved therapeutic efficacy in virusresistant pancreatic cancer cells (ESGCT 2021) - "For this study, we selected the rat parvovirus H1 (H1PV) that is nonpathogenic in humans and has a natural oncolytic activity in several cancer models...To our knowledge, we report here for the first time the production of highly selective and potent OV using directed evolution to override PDAC resistance to virotherapy. While the molecular mechanisms involved are still under investigation, this project is a first step towards precision medicine strategies based on OV"

Clinical • IO biomarker • Oncolytic virus • Brain Cancer • Gastrointestinal Cancer • Gene Therapies • Glioma • Hepatology • Infectious Disease • Oncology • Pancreatic Cancer • Solid Tumor

Oncolytic H-1 parvovirus binds to sialic acid on laminins for cell attachment and entry. (PubMed, Nat Commun) - "We also provide evidence of a direct correlation between LAMC1 expression levels and H-1PV oncolytic activity in 59 cancer cell lines and in 3D organotypic spheroid cultures with different sensitivities to H-1PV infection. These results support the idea that tumours with elevated levels of γ1 containing laminins are more susceptible to H-1PV-based therapies."

Journal • Oncolytic virus • Brain Cancer • Glioblastoma • Infectious Disease • Oncology • Solid Tumor

Human Retrotransposons and the Global Shutdown of Homeostatic Innate Immunity by Oncolytic Parvovirus H-1PV in Pancreatic Cancer. (PubMed, Viruses) - "This way of suppression may compromise the interferogenicity of drugs having gemcitabine-like mechanisms of action. This shortcoming in immunogenic cell death induction is however amendable by immune cells which release IFN in response to H-1PV."

Clinical • Journal • Oncolytic virus • Gastrointestinal Cancer • Hepatology • Immune Modulation • Inflammation • Oncology • Pancreatic Cancer • Solid Tumor

Oncolytic viruses as a promising therapeutic strategy against the detrimental health impacts of air pollution: The case of glioblastoma multiforme. (PubMed, Semin Cancer Biol) - "Engineered adenoviruses (i.e., DNX-2401, DNX-2440, CRAd8-S-pk7 loaded Neural stem cells), herpes simplex virus type 1 (i.e., HSV-1 C134, HSV-1 rQNestin34.5v.2, HSV-1 G207, HSV-1 M032), measles virus (i.e., MV-CEA), parvovirus (i.e., ParvOryx), poliovirus (i.e., Poliovirus PVSRIPO), reovirus (i.e., pelareorep), moloney murine leukemia virus (i.e., Toca 511 vector), and vaccinia virus (i.e., vaccinia virus TG6002) as possible life-changing alleviations for GBM have been discussed. We believe that the article will significantly appeal to a broad readership of virologists, oncologists, neurologists, environmentalists, and those who work in the field of (bio)energy. Policymakers may also use it to establish better health policies and regulations about air pollution and (bio)fuels exploration, production, and consumption."

Clinical • Journal • Oncolytic virus • Brain Cancer • Glioblastoma • Glioma • Hematological Malignancies • Herpes Simplex • Immunology • Infectious Disease • Inflammation • Leukemia • Oncology • Solid Tumor

Parvovirus-Based Combinatorial Immunotherapy: A Reinforced Therapeutic Strategy against Poor-Prognosis Solid Cancers. (PubMed, Cancers (Basel)) - "This review deals with the smallest among all OVs, the H-1 parvovirus (H-1PV), and focuses on H-1PV-based combinatorial approaches, whose efficiency has been proven in preclinical and/or clinical settings. Special focus is given to cancer types with the most devastating impact on life expectancy that urgently call for novel therapies."

Journal • Review • Colorectal Cancer • Gastrointestinal Cancer • Glioblastoma • Hepatology • Immune Modulation • Immunology • Inflammation • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor

Oncolytic H-1 Parvovirus Enters Cancer Cells through Clathrin-Mediated Endocytosis. (PubMed, Viruses) - "We also show that H-1PV entry is dependent on dynamin, while viral trafficking occurs from early to late endosomes, with acidic pH necessary for a productive infection. This is the first study that characterises the cell entry pathways of oncolytic H-1PV."

Journal • Oncolytic Virus • Cervical Cancer • Gastrointestinal Cancer • Glioblastoma • Glioma • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Immune Conversion of Tumor Microenvironment by Oncolytic Viruses: The Protoparvovirus H-1PV Case Study. (PubMed, Front Immunol) - "As a case study we focus on the rodent protoparvovirus H-1PV and its dual role as an oncolytic and immune modulatory agent. Potential strategies to improve H-1PV anticancer efficacy are also discussed."

Biomarker • Clinical • Journal • Oncolytic Virus • Review • Tumor microenvironment • Immune Modulation • Inflammation • Oncology

Immune System Stimulation by Oncolytic Rodent Protoparvoviruses. (PubMed, Viruses) - "The molecular mechanisms of PV-induced immunostimulation are also discussed. Furthermore, initial encouraging in-human observations from clinical trials and compassionate virus uses are presented, and speak in favor of further H-1PV clinical development as partner drug in combined immunotherapeutic protocols."

Journal • Preclinical • Review • Immune Modulation • Inflammation • Oncology

H-1 Parvovirus as a Cancer-Killing Agent: Past, Present, and Future. (PubMed, Viruses) - "Thus, further studies are needed to improve H-1PV's anticancer profile. In this review, we describe H-1PV's anticancer properties and discuss recent efforts to improve the efficacy of H-1PV and, thereby, the clinical outcome of H-1PV-based therapies."

Journal • Review • Brain Cancer • Gastrointestinal Cancer • Glioma • Oncology • Pancreatic Cancer • Solid Tumor