A5060991985- Nanoplatforms for cancer theranostics
- Hepatocellular Carcinoma Treatment and Prognosis
- Cardiac and Coronary Surgery Techniques
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Research and Treatments
- Animal Virus Infections Studies
- Immunotherapy and Immune Responses
Transgene (France)
2024-2025
Abstract Background: Effective treatment for patients with metastatic cancer is limited, particularly colorectal liver lesions (mCRC), where accessibility to numerous tumours essential favourable clinical outcomes. Oncolytic viruses (OVs) selectively replicate in cells; however, direct targeting of inaccessible limited when using conventional intravenous or intratumoural administration routes. Methods: We conducted a multi-centre, dose-escalation, phase I study vaccinia virus, TG6002, via...
<p>AEs summarized by relationship to grade.</p>
<p>AEs summarized by relationship to TG6002 and 5-FC.</p>
<p>Adaptive T-cell responses to treatment. function was assessed by ELISpot assay, which showed an IFNγ-release response CEA and TG6002. <b>A,</b> Data expressed as the mean fold change ± SEM SFU of post-treatment samples compared with baseline. <i>n</i> = 6 patients, sample availability–dependent. <b>B,</b> Representative examples from two patients showing BS samples, in triplicate, depicting <b>C</b> <b>D,</b> TCRβ...
<p>Immunophenotyping patient PBMCs</p>
<p>mRNA sequencing of patient PBMCs revealing clustering DEGs involved in immune activation and response pathways to treatment. <b>A,</b> The number upregulated ssDEGs the post-treatment samples relative pretreatment controls for days 2 15 post-infusion. <b>B,</b> Volcano plots three patients that highlight nine commonly expressed (red: downregulated DEGs, blue: black: nonsignificant changes green: specific highlighted ssDEGs). <b>C,</b> Cluster plot...
<p>Trial schema and sampling schedule. <b>A,</b> Trial depicting treatment schedule of two planned cycles IHA TG6002 oral 5-FC. <b>B,</b> Patient blood tissue samples taken at various time points prior to during treatment. Blood were specific for downstream analyses: translational (red), pharmacokinetic (blue), pharmacodynamic (green), neutralizing antibody (purple), biopsies (black). SC, screening; BS, baseline; C, cycle; D, day. (Created with <a...
<div>AbstractPurpose:<p>Effective treatment for patients with metastatic cancer is limited, particularly those colorectal liver lesions, in which accessibility to numerous tumors essential favorable clinical outcomes. Oncolytic viruses (OV) selectively replicate cells; however, direct targeting of inaccessible lesions limited when using conventional intravenous or intratumoral administration routes.</p>Patients and Methods:<p>We conducted a multicenter,...
<p>Detection of TG6002 in patient tumor biopsies. <b>A,</b> Table summary data collated from assays to detect the presence biopsies: qPCR and qRT-PCR viral nucleic acids, plaque assay replication-competent virus (infectious particles per biopsy), IHC determine protein, 5-FU (pg/mg) demonstrate transgene activity. Samples are designated as either positive or negative/below limit detection for each assay. <b>B,</b> Representative examples positively stained cells...
<p>Detection of TG6002, nAb, 5-FC, 5-FU, and F-BAL in plasma following treatment. <b>A,</b> Plasma samples analyzed by qPCR to detect TG6002 Values stated are the number copies per milliliter (c/mL). <b>B,</b> Serum nAb titers (IC50) for <i>n</i> = 15 patients, sample availability–dependent. * <i>P</i> < 0.05, paired <i>t</i> test. <b>C,</b> concentrations at day 8 treatment (<i>n</i> 13 patients),...
<p>Activation of patient peripheral immune responses following treatment. <b>A,</b> CRT concentration (ng/mL) in plasma measured by ELISA. Data are expressed as the mean ± SEM; <i>n</i> = 14 patients, sample availability–dependent. * <i>P</i> < 0.05, paired <i>t</i> test. <b>B,</b> Immunophenotyping PBMCs for expression CD69 and PD-L1. Relevant cell populations depicted each plot. fold change 9 patients....
ABSTRACT Background Effective treatment for patients with metastatic cancer is limited, particularly colorectal liver lesions (mCRC), where accessibility to numerous tumours essential favourable clinical outcomes. Oncolytic viruses (OVs) selectively replicate in cells; however, direct targeting of inaccessible limited when using conventional intravenous ( i.v. ) or intratumoural i.t. administration routes. Methods We conducted a multi-centre, dose-escalation, phase I study vaccinia virus,...
Abstract The TG6002.03 trial is a dose-escalation phase 1 clinical of TG6002 infusion via the hepatic artery in patients with liver-dominant colorectal cancer metastases. an engineered Copenhagen strain oncolytic Vaccinia virus, deleted thymidine kinase and ribonucleotide reductase to enhance tumor selective viral replication expressing FCU1, enzyme converting non-cytotoxic prodrug 5-fluorocytosine (5-FC) into chemotherapeutic compound 5-fluorouracil (5-FU). In this trial, advanced...