A physiologically based pharmacokinetic model for V937 oncolytic virus in mice DOI Creative Commons
Sara Peribañez-Dominguez, Zinnia P. Parra‐Guillén,

Tomoko Freshwater

и другие.

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Сен. 13, 2023

Introduction: Oncolytic viruses (OVs) represent a novel therapeutic strategy in oncology due to their capability selectively infect and replicate cancer cells, triggering direct and/or immune-induced tumor lysis. However, the mechanisms governing OV pharmacokinetics are still poorly understood. This work aims develop physiologically based pharmacokinetic model of OV, V937, non-tumor-bearing mice get quantitative understanding its elimination tissue uptake processes. Materials methods: Model development was performed using data obtained from 60 mice. Viral levels were quantified eight tissues after single intravenous V937 dose. An external dataset used for validation. test set included multiple-dose experiments with different routes administration. distribution each organ described physiological structure on mouse-specific blood flows volumes. Analyses non-linear mixed-effects approach NONMEM 7.4. Results: showed drop 10 8 5 copies/µg RNA at day 1 blood, reflected high estimate total clearance (18.2 mL/h). A well-stirred provided an adequate description all organs except muscle heart, where saturable process improved description. The highest numbers viral copies observed brain, lymph node, kidney, liver, lung, spleen first injection. On other hand, maximum amount muscle, pancreas occurred 3 days Conclusion: To best our knowledge, this is developed characterize biodistribution, representing relevant source knowledge regarding vivo behavior OVs. can be further expanded by adding compartment, OVs could replicate.

Язык: Английский

Characterization of VSV-GP Morphology by CryoEM Imaging and SEC-MALS DOI Creative Commons
Dongyue Xin,

Leela Kurien,

Kevin Briggs

и другие.

Molecular Therapy — Methods & Clinical Development, Год журнала: 2025, Номер 33(1), С. 101429 - 101429

Опубликована: Фев. 6, 2025

Vesicular stomatitis virus expressing the glycoprotein of lymphocytic choriomeningitis (VSV-GP) is a promising platform for oncolytic viruses and cancer vaccines. In this work, cryoelectron microscopy (cryo-EM) imaging was employed to directly visualize VSV-GP particles. Several different subpopulations particle morphology were observed. Definition fraction counting enabled quantitative comparison subpopulation profiles between several samples. developing an orthogonal method with higher throughput, we showed that morphological profile particles can be characterized by size exclusion chromatography coupled multi-angle light scattering detector (SEC-MALS) based on novel shape-based separation mechanism. Together, two complementary techniques enable analysis potentially other non-spherical or nanoparticles.

Язык: Английский

Процитировано

2
Molecular Pathology Methods to Characterize Biodistribution and Pharmacodynamics of the Oncolytic Virus VSV-GP in a Nonclinical Tumor Model DOI
Andrea Matter, Karol Budzik,

Saurin Mehta

и другие.

Toxicologic Pathology, Год журнала: 2025, Номер 53(1), С. 65 - 82

Опубликована: Янв. 1, 2025

Replication-competent oncolytic virus (OV) therapies are a promising new modality for cancer treatment. However, they pose unique challenges preclinical assessment, due in part to their tumor specificity and ability self-replicate vivo. Understanding biodistribution, immune cell responses, potential effects of intratumoral replication on these outcomes important aspects the nonclinical profile OVs. Herein, single intravenous dose vesicular stomatitis pseudotyped with glycoprotein lymphocytic choriomeningitis (VSV-GP), or cargo-expressing variant (VSV-GP-[cargo]), was examined both tumor-free CT26.CL25.IFNAR -/- syngeneic tumor-bearing mouse models. Biodistribution responses were characterized using different molecular pathology methods, including strand-specific situ hybridization method differentiate administered viral genomes from replicated transcribed anti-genome RNA. We identified distinct patterns biodistribution across nontumor sites but no major differences off-tumor tropism, between Our findings characterize key cellular changes following systemic exposure VSV-GP, provide better understanding permissive model OV demonstrate how current methods can bridge traditional readouts.

Язык: Английский

Процитировано

0
Advances in the Drug Development and Quality Evaluation Principles of Oncolytic Herpes Simplex Virus DOI Creative Commons

Basma Eid Abdullah Ghorab,

Tongtan Liu, Min Ying

и другие.

Viruses, Год журнала: 2025, Номер 17(4), С. 581 - 581

Опубликована: Апрель 18, 2025

Oncolytic herpes simplex virus (oHSV) represents a promising therapeutic approach to treating cancers by virtue of its selective replication in and lysis tumor cells, with stimulation host antitumor immunity. At present, four OV drugs have been approved for the treatment worldwide, two which are oHSV that received extensive attention, known as T-VEC Delytact. This review discusses history, mechanism action, clinical development, quality control, evaluation principles products, including viral species genetic modifications improved these products’ potential, limitations, future directions. Integration oHSVs immunotherapeutic agents conventional therapies has field malignant tumors. Although much progress achieved, there is still work be done regarding optimization protocols control oncolytic drugs. The approval various underlines their relevance, safety, efficacy, thereby paving way further research aimed at overcoming existing limitations enhancing patient responses.

Язык: Английский

Процитировано

0
Absolute quantification of viral proteins from pseudotyped VSV-GP using UPLC-MRM DOI Creative Commons
Rajeswari Basu, Richard Dambra, Di Jiang

и другие.

Microbiology Spectrum, Год журнала: 2024, Номер 12(8)

Опубликована: Июнь 25, 2024

The rapidly developing field of oncolytic virus (OV) therapy necessitates the development new and improved analytical approaches for characterization during production development. Accurate monitoring absolute quantification viral proteins are crucial OV product can facilitate understanding infection, immunogenicity, stages replication. Targeted mass spectrometry methods like multiple reaction (MRM) offer a robust way to directly detect quantify specific targeted represented by surrogate peptides. We have leveraged power MRM combining ultra-high performance liquid chromatography (UPLC) with Sciex 6500 triple-stage quadrupole spectrometer develop an assay that accurately absolutely quantifies structural pseudotyped vesicular stomatitis (VSV) intended use as biotherapeutic (designated hereafter VSV-GP differentiate it from native VSV). UPLC-MRM method provides heavy-labeled reference standard When added in known exact amounts standards samples, normalize account any small perturbations sample preparation and/or instrument performance, resulting accurate precise quantification. Because multiplexed nature MRM, all quantified at same time. optimized has been enhanced ratios processed GP1 GP2 while simultaneously measuring remaining or unprocessed form envelope protein GP complex (GPC; full-length GPC).

Язык: Английский

Процитировано

1
Characterization of the Anti-Viral and Vaccine-Specific CD8+ T Cell Composition upon Treatment with the Cancer Vaccine VSV-GP DOI Creative Commons

Tamara Hofer,

Lisa Pipperger,

Sarah Danklmaier

и другие.

Vaccines, Год журнала: 2024, Номер 12(8), С. 867 - 867

Опубликована: Авг. 1, 2024

Numerous factors influence the magnitude and effector phenotype of vaccine-induced CD8+ T cells, thereby potentially impacting treatment efficacy. Here, we investigate effect vaccination dose, route immunization, presence a target antigen-expressing tumor, heterologous prime-boost with peptide vaccine partner following antigen-armed VSV-GP. Our results indicate that higher dose increases antigen-specific cell proportions while altering phenotype. The intravenous induces highest proportion cells together lowest anti-viral response followed by intraperitoneal, intramuscular, subcutaneous routes. Moreover, B16-OVA tumor serves as pre-prime, increasing OVA-specific upon thus ratio anti-tumor versus cells. Interestingly, tumor-specific exhibit different compared to bystander Finally, combination viral elicits in tumor-draining lymph nodes. In summary, provide basic immune characterization various affect target-specific phenotypes, enhancing our vaccinology knowledge for future regimen designs.

Язык: Английский

Процитировано

0
Absolute Quantification of Viral Proteins from Pseudotyped Vesicular Stomatitis Virus (VSV-GP) using Ultra High-Performance Liquid Chromatography- Multiple Reaction Monitoring (UPLC-MRM) DOI Creative Commons
Rajeswari Basu, Richard Dambra, Di Jiang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Окт. 10, 2023

ABSTRACT The rapidly developing field of oncolytic virus (OV) therapy necessitates development new and improved analytical approaches for characterization the during production development. Accurate monitoring absolute quantification viral proteins is crucial OV product can facilitate understanding infection, immunogenicity, stages replication. Targeted mass spectrometry methods, like multiple reaction (MRM), offers a robust way to directly detect quantify specific targeted represented by surrogate peptides. We have leveraged power MRM combining ultra-high performance liquid chromatography (UPLC) with Sciex 6500 triple stage quadrupole spectrometer develop an assay that accurately absolutely quantifies structural pseudotyped vesicular stomatitis intended use as biotherapeutic (designated hereafter VSV-GP) differentiate it from native VSV. UPLC-MRM method provides heavy labeled reference standard When added in known exact amounts standards samples, normalize account any small perturbations sample preparation and/or instrument performance, resulting accurate precise quantification. Because multiplexed nature all are quantified at same time. optimized has been enhanced ratios processed GP1 GP2 while simultaneously measuring remaining or unprocessed form envelope protein GPC (full-length GPC). IMPORTANCE Development gained considerable momentum recent years. VSV-GP emerging platform. Novel assays precisely necessity successful vector biotherapeutic. developed based concentrations different VSV-GP. complete processing pre-requisite infectivity virus. extends potential quantifying full-length GPC, which (along separately). used this tracking HEK-293-F cell lines infected

Язык: Английский

Процитировано

0
A physiologically based pharmacokinetic model for V937 oncolytic virus in mice DOI Creative Commons
Sara Peribañez-Dominguez, Zinnia P. Parra‐Guillén,

Tomoko Freshwater

и другие.

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Сен. 13, 2023

Introduction: Oncolytic viruses (OVs) represent a novel therapeutic strategy in oncology due to their capability selectively infect and replicate cancer cells, triggering direct and/or immune-induced tumor lysis. However, the mechanisms governing OV pharmacokinetics are still poorly understood. This work aims develop physiologically based pharmacokinetic model of OV, V937, non-tumor-bearing mice get quantitative understanding its elimination tissue uptake processes. Materials methods: Model development was performed using data obtained from 60 mice. Viral levels were quantified eight tissues after single intravenous V937 dose. An external dataset used for validation. test set included multiple-dose experiments with different routes administration. distribution each organ described physiological structure on mouse-specific blood flows volumes. Analyses non-linear mixed-effects approach NONMEM 7.4. Results: showed drop 10 8 5 copies/µg RNA at day 1 blood, reflected high estimate total clearance (18.2 mL/h). A well-stirred provided an adequate description all organs except muscle heart, where saturable process improved description. The highest numbers viral copies observed brain, lymph node, kidney, liver, lung, spleen first injection. On other hand, maximum amount muscle, pancreas occurred 3 days Conclusion: To best our knowledge, this is developed characterize biodistribution, representing relevant source knowledge regarding vivo behavior OVs. can be further expanded by adding compartment, OVs could replicate.

Язык: Английский

Процитировано

0